Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.53132615
We demonstrate that leptin binding to OB R stimulates formation of STAT 1 and STAT 3 complexes , thereby defining transcriptional motifs for genes that are under leptin control . 0.53132615^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.63285961
Leptin exerts its effects by interacting with specific membrane receptors ( Ob R ) . 0.63285961^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.51770802
Leptin binds to the leptin receptor , present in the hypothalamus and in many other tissues , and modulates energy balance and maintenance of body weight . 0.51770802^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.84671508
Leptin circulates as a free ( FL ) and a protein bound ( BL ) form , with the soluble leptin receptor ( LR ) as an important binding compound . 0.84671508^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.63643178
These data indicate that leptin binds the bovine leptin receptor with high affinity and that a pool of leptin is bound to abundant cell membrane associated proteins . 0.63643178^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Obesity : leptin receptor weighs in . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The cloning of ob , and the demonstration that it encodes a secreted protein ( leptin ) that binds specifically to a receptor ( OB R ) in the brain , have validated critical aspects of this hypothesis . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Researchers nail down leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Evidence that the diabetes gene encodes the leptin receptor : identification of a mutation in the leptin receptor gene in db / db mice . ^^^ OB R is a high affinity receptor for leptin , an important circulating signal for the regulation of body weight . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Abnormal splicing of the leptin receptor in diabetic mice . ^^^ A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6 cM interval on mouse chromosome 4 as db . ^^^ This suggests that the weight reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Phenotype linked amino acid alteration in leptin receptor cDNA from Zucker fatty ( fa / fa ) rat . ^^^ Reported herein are the cloning and sequencing of one of spliced variant forms of rat leptin receptor ( OB R ) cDNA with a short intracellular domain . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The hypothalamic leptin receptor in humans : identification of incidental sequence polymorphisms and absence of the db / db mouse and fa / fa rat mutations . ^^^ Leptin receptor gene expression in hypothalamic tissue from lean and obese humans was examined . ^^^ The full length leptin receptor , that is believed to transmit the leptin signal , is expressed in human hypothalamus . ^^^ There was no difference in the amount of leptin receptor mRNA In seven lean ( BMI 23 . 3 + / 0 . 9 kg / m2 ) and eight obese ( BMI 36 . 9 + / 1 . 5 ) subjects as determined by reverse transcription polymerase chain reaction . ^^^ A sequence polymorphism ( A > G ) was detected at position 668 of the leptin receptor cDNA . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor missense mutation in the fatty Zucker rat . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Localization of leptin receptor mRNA and the long form splice variant ( Ob Rb ) in mouse hypothalamus and adjacent brain regions by in situ hybridization . ^^^ Expression of the leptin receptor gene has been examined in mouse hypothalamus and other brain regions by in situ hybridization . ^^^ A probe specific to the long splice variant of the leptin receptor ( Ob Rb ) , containing the putative intracellular signaling domain , again revealed strong expression in the hypothalamus ; there was , however , minimal hybridization to choroid plexus and leptomeninges . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Phenotype of fatty due to Gln269Pro mutation in the leptin receptor ( Lepr ) . ^^^ It has been shown that db alleles carry mutations in the Lepr ( leptin receptor ) gene . ^^^ Transient transfection studies indicate that the mutant Lepr cDNA has greatly reduced binding of leptin ( Lep ) at the cell surface . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Defective STAT signaling by the leptin receptor in diabetic mice . ^^^ We cloned a long isoform of the wild type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription ( STAT ) 3 , STAT 5 , and STAT 6 . ^^^ Leptin and its receptor , obese receptor ( OB R ) , comprise an important signaling system for the regulation of body weight . ^^^ These data provide further evidence that the mutation in OB R causes the db / db phenotype and identify three STAT proteins as potential mediators of the anti obesity effects of leptin . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We demonstrate the expression of leptin receptor mRNA in primary rat pancreatic islets and in the insulinoma cell line beta TC 3 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Substitution at codon 269 ( glutamine > proline ) of the leptin receptor ( OB R ) cDNA is the only mutation found in the Zucker fatty ( fa / fa ) rat . ^^^ We recently cloned one of spliced variant forms of rat leptin receptor ( OB R ) , which contains a short intracellular domain , and found obese phenotype linked nucleotide alteration in the extracellular domain of the cDNA from the Zucker ( fa / fa ) rat , which results in a glutamine 269 to proline 269 amino acid substitution . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The full length leptin receptor has signaling capabilities of interleukin 6 type cytokine receptors . ^^^ The leptin receptor ( OB R ) is a single membrane spanning protein that mediates the weight regulatory effects of leptin ( OB protein ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
At present , extensive investigations of the roles of leptin and the leptin receptor in human adiposity are in progress . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Molecular cloning of rat leptin receptor isoform complementary DNAs identification of a missense mutation in Zucker fatty ( fa / fa ) rats . ^^^ We cloned the full length rat leptin receptor ( Ob R ) isoform complementary DNAs ( cDNAs ) and examined the gene expression in rats . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
A novel leptin receptor isoform in rat . ^^^ Five mouse and human leptin receptors ( Ob R ) have recently been identified , a long isoform ( Ob Rb ) , preferentially expressed in hypothalamus , and 4 short isoforms , Ob Ra , Ob Rc , Ob Rd , and Ob Re . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor ( Ob R ) is found in many tissues in several alternatively spliced forms raising the possibility that leptin exerts effects on many tissues including the hypothalamus . ^^^ Leptin injection activated Stat 3 but no other STAT protein in the hypothalamus of ob / ob and wild type mice but not db / db mice , mutants that lack an isoform of the leptin receptor . ^^^ Our data indicate the hypothalamus is a direct target of leptin action and that this activation is critically dependent on the gp 130 like leptin receptor isoform missing in C57BLKS / J db / db mice . ^^^ The activation of STAT proteins in response to leptin was assayed in a variety of mouse tissues known to express Ob R . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To investigate the anatomic basis for these effects , we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants . ^^^ Leptin receptor mRNA was densely concentrated in the arcuate nucleus , with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We have cloned three splice variants of a novel cytokine receptor from human hematopoietic stem cells expressing the CD 34 antigen , one of which is identical to the leptin receptor . ^^^ Expression analysis revealed that the leptin receptor is expressed in both human and murine hematopoietic stem cell populations , and that leptin is expressed by hematopoietic stroma . ^^^ Analysis of db / db mice , in which the leptin receptor is truncated , revealed that the steady state levels of peripheral blood B cells and CD 4 expressing T cells were dramatically reduced , demonstrating that the leptin pathway plays an essential role in lymphopoiesis . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Several putative leptin binding proteins were detected by leptin affinity chromatography of which either 80 or 100 kD proteins could be the soluble leptin receptor as approximately 10 % of the bound 125I leptin was immunoprecipitable with leptin receptor antibodies . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
A mutation in the leptin receptor gene is responsible for the obese phenotype of db / db mice . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus . ^^^ Leptin , the protein product of the adipose tissue specific ob ( obese ) gene ( 1 ) , reduces the body weight , adiposity and food intake of obese ob / ob mice on peripheral or central injection ( 2 , 3 , 4 ) . [ 125I ] leptin binding has been detected in mouse choroid plexus ( 5 ) , from which a leptin receptor gene was expression cloned ( 5 ) . ^^^ Leptin receptor mRNA was localized in the hypothalamus by in situ hybridization being particularly abundantly expressed in the arcuate nucleus ( 8 ) . ^^^ Here we report dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus , where the majority of cells examined expressed both genes . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Using degenerate oligonucleotides to the common WSXWS motif , we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone , leptin . mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and murine hemopoietic organs , and a subset of cells from these tissues bound leptin at the cell surface . ^^^ Ectopic expression in murine Ba / F3 and M 1 cell lines revealed that the long , but not the short , form of the leptin receptor can signal proliferation and differentiation , respectively . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
At present , extensive investigations of the roles of leptin and the leptin receptor in human adiposity are in progress . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB R . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Identification of the OB ( leptin ) receptor ( OBR ) as the gene that is defective in diabetes ( Leprdb ) mice and fatty ( Leprfa ) rats provides an important candidate gene for the study of the genetics of human obesity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Localization of leptin receptor mRNA expression in mouse brain . ^^^ The distribution of the leptin receptor in the brain of C 57 mice was investigated using a non radioactive in situ hybridization method . ^^^ Leptin receptor mRNA expression was highest in the arcuate nucleus and median eminence of the hypothalamus , but it was also abundant in hippocampus , primarily in the dentate gyrus and CA 1 , and was detected at low levels in piriform cortex and the medial margin of the medial habenular nucleus . ^^^ The localization of leptin receptor containing neurones in the present study indicates the possibility that the leptin receptor is expressed on neuropeptide Y containing neurones . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Since leptin receptor mRNA has been detected in the ovary , this study was designed to test the hypothesis that leptin may impair granulosa cell ( GC ) estradiol 17 beta ( E 2 ) production by a direct mechanism . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Overlapping and distinct signals through leptin receptor ( OB R ) and a closely related cytokine signal transducer , gp 130 . ^^^ The structure of leptin receptor ( OB R ) is highly homologous to that of gp 130 , the common signal transducing receptor component for the interleukin 6 family of cytokines . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Human blood brain barrier leptin receptor . ^^^ These results provide evidence for a leptin receptor that mediates saturable , specific , temperature dependent binding and endocytosis of leptin at the human blood brain barrier . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To investigate the direct effects of leptin within the CNS , we injected 3 . 5 microg of either mouse or human leptin into the third ventricle ( ICV ) of lean Long Evans rats or obese ( fa / fa ) Zucker rats , in which obesity results from a mutation in the leptin receptor gene . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The coding regions of the cDNA sequences of both leptin and the leptin receptor from NON mice were identical with those of the wild type sequences . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Binding of leptin to the soluble ectodomain of recombinant leptin receptor : a kinetic analysis by surface plasmon resonance . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor ( OB R ) signaling . ^^^ The leptin receptor ( OB R ) mediates the weight regulatory effects of the adipocyte secreted hormone leptin ( OB ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The recently discovered genes for leptin ( ob gene ) and the leptin receptor appear to play a major regulatory role in body energy balance and adipose tissue deposition . ^^^ Furthermore , defects in the ob gene and leptin receptor gene have been demonstrated to be the cause of obesity in several rodent models . ^^^ This review will summarize the current findings on the ob gene , leptin and the leptin receptor in both animals and humans . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion . ^^^ We show that the full length leptin receptor ( Ob Rb ) , which is believed to transmit the leptin signal , is expressed in pancreatic islets of ob / ob and wild type mice , as well as in hypothalamus , liver , kidney , spleen , and heart . ^^^ These results provide evidence that a functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction , particularly from abdominal adipose tissue , may modify directly both basal and glucose stimulated insulin secretion . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Recently , the leptin receptor ( OB R ) was identified and shown to exhibit sequence homology and functional similarity to members of the class 1 cytokine receptor family . ^^^ Leptin and OB R : body weight regulation by a cytokine receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Although the leptin concentrations covered a large range , there were no subgroups of diabetic subjects with very high or low leptin levels that would suggest mutations in the leptin gene or leptin receptor gene comparable to the obese diabetic ob / ob and db / db mice models respectively . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In animal models obesity can be caused by leptin deficiency or by a dysfunction of the hypothalamic leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Phenotype of the obese Koletsky ( f ) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor ( Lepr ) : evidence for deficient plasma to CSF transport of leptin in both the Zucker and Koletsky obese rat . ^^^ The obese phenotypes of the diabetes ( db ) mouse and fatty fa ) rat are due to functional null mutations of the leptin receptor ( Lepr ) . ^^^ However , equivalent CSF leptin concentration between lean and obese rats ( fa / fa , f / f ) indicates that leptin can enter the CSF through a non Lepr mediated mechanism , which may be saturated at normal physiological plasma leptin concentration . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin treated obese ( ob / ob ) and cold exposed lean mice . ^^^ Leptin receptor gene expression has been measured in arcuate and ventromedial hypothalamic nuclei . ^^^ Twice daily leptin administration for 7 days profoundly affected food intake , reduced leptin receptor mRNA in the arcuate nucleus , and had a similar effect on neuropeptide Y gene expression . ^^^ Exposure of lean mice to cold for 24 h caused an induction of leptin receptor and NPY mRNA which was normalized when animals were returned to the warm . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor ( OB R ) oligomerizes with itself but not with its closely related cytokine signal transducer gp 130 . ^^^ Since the IL 6 family of cytokines signal through gp 130 homodimer or gp130 / LIFR heterodimer , we have examined in this study the possible involvement of gp 130 and LIFR in leptin signaling through OB R . ^^^ Ba / F3 cells , which do not express gp 130 , are non responsive to leptin and exhibit increased DNA synthesis in response to leptin after transfection of OB R cDNA alone . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin . ^^^ This molecule was used to identify high affinity binding sites on human embryonic 293 kidney cells and subsequently to isolate a cDNA encoding the leptin receptor from this cell line by expression cloning . ^^^ This receptor corresponds to the short form of the recently isolated leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well fed and feed restricted ewes . ^^^ Leptin , produced by adipocytes , has receptors in the hypothalamus , but more precise locations of leptin receptor expressing cell bodies have not been reported in a livestock species . ^^^ The leptin receptor transcript has several splice variants in the mouse and human , but only the `` long form ' ' product ( OBRL ) is capable of signal transduction . ^^^ A partial ovine long form leptin receptor cDNA was cloned and used to evaluate OBRL mRNA expression within hypothalamic , anterior pituitary , and adipose tissues of ovariectomized adult ewes . ^^^ These findings provide evidence that the full length leptin receptor is expressed in hypothalamic , anterior pituitary , and adipose tissue ( the latter proffering an autoregulatory mechanisms for leptin ) and that within the hypothalamus , this receptor form is differentially expressed in well fed vs . feed restricted animals . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor gene ( LEPR ) maps to porcine chromosome 6 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor ( LEPR ) gene maps to bovine chromosome 3q33 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
A short form of leptin receptor performs signal transduction . ^^^ Several alternate spliced isoforms ( a e , as well as others ) of the leptin receptor ( OBR ) have been cloned , all of which , except for OBRe ( soluble form ) , contain a single transmembrane domain . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression and localization of the leptin receptor in endocrine and neuroendocrine tissues of the rat . ^^^ To determine whether endocrine and neuroendocrine tissues could be targets for leptin action , we examined whether these tissues express the leptin receptor mRNA by utilizing reverse transcription polymerase chain reaction ( RT PCR ) analysis in selected tissues from the male and female rat . ^^^ The results revealed that the leptin receptor mRNA transcript is highly expressed in the ovary , uterus and testis , moderately expressed in the hypothalamus and anterior pituitary , with low to no expression in the adrenal . ^^^ Furthermore , immortalized GnRH ( GT 1 7 and NLT ) neurons and ovarian granulosa cells were also demonstrated by RT PCR analysis to express the leptin receptor , suggesting that GnRH neurons and steroid producing cells of the ovary could be targets for leptin action . ^^^ Immunohistochemical studies revealed dense immunolocalization of the leptin receptor in the choroid plexus , and interestingly , in the arcuate nucleus / median eminence of the female rat a key sit in the control of feeding and reproduction . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor activates janus kinase 2 and signals for proliferation in a factor dependent cell line . ^^^ The antiobesity effects of leptin are mediated by the obese receptor ( OB R ) , a member of the cytokine receptor superfamily . ^^^ These results provide further support for the long isoform , OB Rb , being the principal mediator of the effects of leptin and help to explain why db / db mice are resistant to leptin , despite the presence of the short OB R isoforms . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The db gene encodes the leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In islets of obese Zucker Diabetic Fatty rats with leptin receptor mutations , leptin had no effect in vivo or in vitro . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus relationship with NPY neurones . ^^^ Leptin receptors were recently cloned and a mutation in the leptin receptor gene in obese db / db mice was identified . ^^^ Leptin receptor mRNA has been detected in brain , including hypothalamus , but the cellular localization has so far not been clarified . ^^^ Here we report on the cellular localization of leptin receptor mRNA in the mouse brain using in situ hybridization . ^^^ Within the arcuate nucleus , cell bodies expressing leptin receptor mRNA were distributed in its ventromedial subdivision . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT PCR and in situ hybridization . ^^^ Expression of leptin receptor splice variants , including the long form variant ( Ob Rb ) , has been examined in murine peripheral tissues . ^^^ RT PCR indicates that the leptin receptor , Ob R , and in particular the Ob Ra splice variant are expressed in a wide range of tissues . ^^^ However , the long form leptin receptor , Ob Rb , was only expressed at significant levels in the medulla of the adrenal and the inner zone of the medulla of the kidney . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Understanding of the biologic basis of obesity has grown rapidly in the last few years , especially with the identification of a novel endocrine pathway involving the adipose tissue secreted hormone leptin and the leptin receptor that is expressed in the hypothalamus . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Upregulation of leptin receptor mRNA expression in obese mouse brain . ^^^ Leptin receptor gene expression in the brains of lean ( + / + ) and obese ( ob / ob ) C57Bl / 6 mice was examined using a non radioactive in situ hybridization detection method . ^^^ Significant increases in leptin receptor mRNA expression were found in the ventromedial and arcuate hypothalamic nuclei , piriform and olfactory cortices and medial habenular nucleus . ^^^ There were very minor changes in the amount of leptin receptor mRNA expression in hippocampus proper ( CA 1 3 ) . ^^^ Results indicated that leptin receptor is upregulated when there is a lack of functional leptin , as in hereditary obese ( ob / ob ) mice . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Amino acid variants in the human leptin receptor : lack of association to juvenile onset obesity . ^^^ In this study we tested the hypothesis that juvenile onset obesity in humans may be caused by leptin resistance mediated through genetic variations in isoforms of the hypothalamic leptin receptor . ^^^ In conclusion , it is unlikely that mutations in the coding region of the long isoform of the leptin receptor are a common cause of juvenile onset obesity . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We have physically localized the human leptin receptor gene ( LEPR ) to a region at 1p31 , between the anonymous microsatellite markers D1S515 and D1S198 . ^^^ Since the leptin receptor gene is a candidate gene for obesity , and because of its proximity to D1S198 , a marker previously linked to insulin secretion , the LEPR gene was sequenced in 20 non diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose . ^^^ Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians . ^^^ The genomic structure of the human leptin receptor gene , corresponding to the published human brain cDNA sequence , spans over 70 kb and includes 20 exons . ^^^ Two of these polymorphisms , Lys109Arg and Gln223Arg , are amino acid substitutions in the extracellular domain of the leptin receptor , one polymorphism is a silent substitution , and four occur in non coding regions of the leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In summary the data provide the first evidence for a positive crosstalk between the signalling chain of the insulin receptor and the leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor mutations in 129 db3J / db3J mice and NIH facp / facp rats . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor of Zucker fatty rat performs reduced signal transduction . ^^^ The fa mutation has been determined to be a missense mutation in the extracellular domain of the leptin receptor . ^^^ We report herein the construction of CHO cells that stably express the fa type leptin receptor and the characterization of this receptor using mRNA expression levels of the immediate early genes , c fos , c jun , and jun B , which are induced by leptin as a criterion of signal transduction . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Here , we show that pancreatic islets express a long ( signal transducing ) form of leptin receptor mRNA and that beta cells bind a fluorescent derivative of leptin ( Cy 3 leptin ) . ^^^ A functional role for the beta cell leptin receptor is indicated by our observation that leptin ( 100 ng / ml ) suppressed the secretion of insulin from islets isolated from ob / ob mice . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor gene variation and obesity : lack of association in a white British male population . ^^^ Rodents with mutations in the leptin receptor gene develop morbid obesity . ^^^ It is possible , therefore , that leptin receptor gene mutations contribute to human obesity . ^^^ To test this possibility , we determined the entire coding sequence of the human leptin receptor cDNA from peripheral blood lymphocytes of 22 morbidly obese patients with body mass index ( BMI ) between 35 . 1 and 60 . 9 kg / m2 . ^^^ These results suggest that mutations in the leptin receptor gene are not a common cause of human obesity . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells , and that mRNAs for CNTF receptor subunits , similarly to the mRNA of leptin receptor , are localized in mouse hypothalamic nuclei involved in the regulation of energy balance . ^^^ Unlike leptin , CNTF also reduced obesity related phenotypes in db / db mice , which lack functional leptin receptor , and in mice with diet induced obesity , which are partially resistant to the actions of leptin . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
As the leptin receptor is present in the kidney , we evaluated the role of the kidney in removing circulating leptin in humans . ^^^
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Anatomic localization of alternatively spliced leptin receptors ( Ob R ) in mouse brain and other tissues . ^^^
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Leptin receptor action in hepatic cells . ^^^ In humans and rodents , two major forms of leptin receptors ( OB R ) are expressed . ^^^
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The leptin receptor promoter controls expression of a second distinct protein . ^^^ The leptin receptor ( OB R ) is a single membrane spanning protein that mediates the weight regulatory effects of leptin ( OB protein ) . ^^^ Here we report evidence for the synthesis of a human mRNA splice variant of the OB R gene that potentially encodes a novel protein , leptin receptor gene related protein ( OB RGRP ) , which displays no sequence similarity to the leptin receptor itself . ^^^ This OB RGRP transcript contains the first two OB R gene 5 ' untranslated exons , but then is alternatively spliced to two novel exons which were mapped to a yeast artificial chromosome containing the leptin receptor gene . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Ligand independent dimerization of the extracellular domain of the leptin receptor and determination of the stoichiometry of leptin binding . ^^^ The leptin receptor is a class 1 transmembrane protein with either a short or a long cytoplasmic domain . ^^^ Cross linking of radiolabeled leptin to different isoforms of the leptin receptor expressed on COS 1 cells reveals leptin receptor monomer , homodimer , and oligomer complexes . ^^^ Cotransfection of the long and short form of the leptin receptor did not provide any evidence for the formation of heterodimer complexes . ^^^ Soluble forms consisting of either the entire extracellular domain or the two cytokine receptor homologous domains of the leptin receptor were purified to homogeneity from recombinant baculovirus infected insect cells by leptin affinity chromatography . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Obese Zucker rats , known to possess a mutation in the gene for the leptin receptor , were resistant to the sympathoexcitatory effects of leptin , despite higher achieved plasma leptin concentrations . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The `` diabetes ' ' ( db ) gene of the mouse codes for a mutated leptin receptor a cue to understanding obesity ? ] . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Several genetic models of animal obesity have been characterized as carriers of mutations of either the ob gene or leptin receptor . ^^^
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Because skeletal muscle expresses the leptin receptor and plays a major role in determining energy metabolism , we studied leptin ' s effects on glucose and fatty acid ( FA ) metabolism in isolated mouse soleus and extensor digitorum longus ( EDL ) muscles . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Hyperlipoproteinemia is one of the phenotypic characteristics of the fat Zucker rat that carries a mutation in the leptin receptor gene . ^^^
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Expression and characterization of a putative high affinity human soluble leptin receptor . ^^^ In addition , differentially spliced leptin receptor messenger RNAs have been identified . ^^^ Functional mutations in either the leptin or leptin receptor gene cause obesity . ^^^ In the present study , expression of the full length human leptin receptor complementary DNA encoding the long cytoplasmic domain of leptin receptor in COS 7 cells resulted in high affinity membrane binding of 125I leptin ( Ki approximately 200 pM ) ; no detectable binding was present in the medium . ^^^ In addition , we expressed the extracellular domain of human leptin receptor in COS 7 cells and identified a soluble leptin receptor in the conditioned medium that binds human and mouse leptin with high affinity comparable with the full length membrane receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In NZO mice , leptin resistance may be the result of decreased transport of leptin into the cerebrospinal fluid , whereas in Ay mice , leptin resistance probably results from defects downstream of the leptin receptor in the hypothalamus . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
This is related to hyperinsulinemia and hypercorticosteronemia induced leptin oversecretion , as well as to central leptin receptor dysfunctions preventing normal leptin access to and action within specific brain areas . ^^^ Lack of leptin ( mutated leptin gene ) or inefficient leptin action ( leptin receptor defect ) results in increased hypothalamic neuropeptide Y levels . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Rapid communication : a restriction fragment length polymorphism in the porcine leptin receptor ( LEPR ) gene . ^^^
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Increase in serum leptin and uterine leptin receptor messenger RNA levels during pregnancy in rats . ^^^ Leptin receptor mRNA levels in the uterus are also regulated with an increase about 2 . 7 fold during this same period , whereas there is no change in other tissues examined . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin had no inhibitory effect on glycogen synthesis in soleus muscle from the diabetic ( db / db ) mice , which lack the functional leptin receptor . ^^^ The full length leptin receptor ( Ob Rb ) , is expressed in soleus muscle of both ob / ob and wild type mice , however with no detectable differences in expression level . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor mRNA is found in a number of central and peripheral locations . ^^^ In the current study , the presence of the leptin receptor was identified on epinephrine secreting cells in the adrenal medulla . ^^^ Immunohistochemical studies found dense leptin receptor like immunoreactivity in the adrenal medulla with no labeling in the adrenal cortex . ^^^ Double immunofluorescent labeling confirmed that the leptin receptor was present on cells that were phenylethanolamine N methyltransferase like immunoreactive and therefore were epinephrine secreting cells . ^^^ Leptin receptor mRNA in the adrenal medulla was detected by reverse transcriptase polymerase chain reaction , with the majority of the mRNA coding for the short isoform ( Ob Ra ) of the receptor . ^^^
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Exonic and intronic sequence variation in the human leptin receptor gene ( LEPR ) . ^^^
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High levels of leptin with increasing food intake and body weight gain signify hypothalamic leptin receptor resistance during the immediate postnatal period . . ^^^
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Detection and quantification of the leptin receptor splice variants Ob Ra , b , and , e in different mouse tissues . ^^^ Ob Ra , b , and e are the major splice forms of the leptin receptor . ^^^
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Hyperleptinemia , leptin resistance , and polymorphic leptin receptor in the New Zealand obese mouse . ^^^ Leptin receptor messenger RNA as detected by PCR appears as abundant in hypothalamic tissue of NZO mice as in tissue from lean mice . ^^^ Ten nucleotide polymorphisms are found in the complementary DNA of the leptin receptor , resulting in two conservative substitutions ( V541I and V651I ) in the extracellular part of the receptor and one nonconservative substitution ( T1044I ) in the intracellular domain between the presumed Jak and STAT binding boxes . ^^^ Thus , the polymorphic leptin receptor seems to play only a minor , if any , role in the obesity and hyperleptinemia of the NZO mouse . ^^^ It is suggested that the main defect in NZO is located distal from the leptin receptor or at the level of leptin transport into the central nervous system . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The expression of the leptin receptor in several hypothalamic nuclei suggests that multiple neuronal subtypes are targets for leptin ' s action . ^^^ Products of the proopiomelanocortin ( POMC ) gene are known to affect feeding behavior , and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus . ^^^ We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor . ^^^ Quantitative analysis confirmed that POMC neurons in the hypothalamus express leptin receptor mRNA . ^^^
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The leptin receptor isoforms , Ob Ra and Ob Rb , are present in the pancreatic beta cell line MIN 6 and in rat pancreatic islets , based on RT PCR . ^^^
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Rat insulinoma derived pancreatic beta cells express a functional leptin receptor that mediates a proliferative response . ^^^ The functional leptin receptor is also present in pancreatic islets and we now demonstrate that a commonly used clonal insulin secreting beta cell line , RINm5F , expresses high levels of the Ob Rb mRNA . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Using both parametric and nonparametric methods , we found no evidence of linkage of obesity to any of nine candidate genes / regions , including the Prader Willi chromosomal region ( PWS ) , the human homologue of the mouse agouti gene ( ASP ) , and the genes for leptin ( OB ) , the leptin receptor ( OBR / DB ) , the beta 3 adrenergic receptor ( ADRB 3 ) , lipoprotein lipase ( LPL ) , hepatic lipase ( LIPC ) , glycogen synthase ( GYS ) , and tumor necrosis factor alpha ( TNFA ) . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of leptin receptor mRNA ( long form splice variant ) in the human cerebellum . ^^^ Primers specific to the long isoform of leptin receptor ( OB Rb ) mRNA were used in reverse transcriptase linked polymerase chain reactions ( RT PCR ) to investigate the expression of this receptor in the hypothalamus and cerebellum of human and rat . ^^^
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Genetic studies of the leptin receptor gene in morbidly obese French Caucasian families . ^^^
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A short form of leptin receptor ( with a cytoplasmic domain of 34 amino residues ) has been identified in the choroid plexus . ^^^ Then leptin binds to a long form of leptin receptor in the hypothalamus ( with a cytoplasmic domain of 302 amino residues ) and decreases the production of neuropeptide Y , a neuromediator of food intake . ^^^ The long form of leptin receptor , transmits its information via the Janus Kinases ( JAK ) who subsequently phosphorylate transcription factors of the STAT family . ^^^ Intermediary forms of leptin receptor have been identified in other tissues : liver , heart , skeletal muscles , endocrine pancreas . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Differential expression of mRNA for leptin receptor isoforms in the rat brain . ^^^ Leptin plays an important role in the control of food intake and energy metabolism by interacting with its receptor ( OB R ) in the brain . ^^^ Finally , the detection of OB R mRNA in a number of other brain regions may indicate the involvement of leptin in additional as yet undefined physiological functions . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor . ^^^ The binding protein was purified and partially sequenced , revealing sequence identity to the extracellular domain of the leptin receptor . ^^^ We found that the placenta produces large amounts of the OB Re isoform of leptin receptor mRNA , which encodes a soluble binding protein . ^^^ Thus , the extreme hyperleptinemia of late pregnancy is attributable to binding of the leptin by a secreted form of the leptin receptor made by the placenta . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Our observations suggest that the leptin receptor mutation fak imposed on a hypertensive background results in extreme hyperinsulinemia , glucose intolerance , and decreased expression of postreceptor insulin signaling proteins in skeletal muscle . ^^^
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Recent evidence suggests that leptin and the leptin receptor are part of a novel pathway which stimulates haemopoiesis . ^^^
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The leptin receptor ( OB R / B219 ) is expressed in a variety of protein isoforms not only in the central nervous system , but also in reproductive , and hematopoietic tissues . ^^^
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The fine structure of the murine leptin receptor gene ( Lepr ) is described . ^^^ Fine structure of the murine leptin receptor gene : splice site suppression is required to form two alternatively spliced transcripts . ^^^ Thus , it is possible that a single leptin receptor molecule could have two functional ligand binding domains . ^^^
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POMC containing neurons express the leptin receptor , and thus it is conceivable that the POMC gene itself may be part of the signaling pathway involved in leptin ' s action on the brain . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Human leptin receptor gene in obese Japanese subjects : evidence against either obesity causing mutations or association of sequence variants with obesity . ^^^ Leptin is an adipocyte derived blood borne satiety factor that acts on its cognate leptin receptor ( Ob R ) in the hypothalamus , thereby regulating food intake and energy expenditure . ^^^
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Using dual in situ hybridization , long isoform leptin receptor ( OB Rb ) was localized to GLP 1 neurons originating in the nucleus of the solitary tract . ^^^
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The Gln223Arg and Lys656Asn polymorphisms in the human leptin receptor do not associate with traits related to obesity . ^^^
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Localization of leptin receptor in the human brain . ^^^
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Leptin ( OB ) , an adipocyte secreted circulating hormone , and its receptor ( OB R ) are key components of an endocrine loop that regulates mammalian body weight . ^^^
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Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta . ^^^ To assess whether leptin is involved in fetal growth and development we have examined the distribution of mRNAs encoding leptin and the leptin receptor ( which has at least six splice variants ) in the 14 . 5 day postcoitus mouse fetus and in the placenta using reverse transcription PCR and in situ hybridization . ^^^ High levels of gene expression for leptin , the leptin receptor , and the long splice variant of the leptin receptor with an intracellular signaling domain were observed in the placenta , fetal cartilage / bone , and hair follicles . ^^^ Western blotting and immunocytochemistry , using specific antibodies , demonstrated the presence of leptin and leptin receptor protein in these tissues . ^^^ These results suggest that leptin may play a role in the growth and development of the fetus , both through placental and fetal expression of the leptin and leptin receptor genes . ^^^
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At present research work focuses on leptin receptor studies and on ob gene polymorphism and its expression in feeding disorders including obesity and anorexia nervosa . ^^^
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The obese Zucker rat ( OZR ) exhibits a missense mutation in the cDNA for the leptin receptor , producing a single amino acid substitution in the extracellular domain of the receptor . ^^^ A mutation in the leptin receptor gene of the db / db mouse prevents the synthesis of the long splice variant of the receptor . ^^^
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The possibility that the leptin receptor ( LEPR ) mediates autocrine regulation of leptin expression in adipose tissue was examined in 10 day old Zucker rat pups with different copy numbers of the leptin receptor mutation ( Lepr ( fa ) ) . ^^^ The leptin receptor mediates apparent autocrine regulation of leptin gene expression . ^^^ Reduced copy number for the functional leptin receptor apparently results in a diminished negative feedback signal to the leptin gene in adipose tissue . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The aim of the present study was to identify the signalling path from the leptin receptor to the PI 3 kinase . ^^^ As we could not detect the long leptin receptor isoform in C2C12 myotubes we conclude that this signalling pathway is activated by a short leptin receptor isoform . . ^^^
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The site of action of leptin is likely to be the hypothalamus , since this area is important in the control of food intake and leptin receptor mRNA is particularly abundant in this area . ^^^
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The long form of the leptin receptor ( OB Rb ) mRNA was present in the islets and insulinoma cell lines . ^^^ Fasted normal and leptin receptor deficient db / db mice showed no response to leptin . ^^^
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Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin receptor ( OB Rb ) , which is present in the hypothalamus and in certain peripheral organs , including adipose tissue . ^^^
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Mutations in leptin or the receptor isoform ( Ob R [ L ] ) present in hypothalamic neurons result in profound obesity and symptoms of non insulin dependent diabetes . ^^^ Our data indicate that the K ( ATP ) channel may function as the molecular end point of the pathway following leptin activation of the Ob R ( L ) receptor in hypothalamic neurons . . ^^^
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The leptin receptor may exist in pancreatic islets . ^^^
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We found the leptin receptor to be expressed in insulin and glucagon secretin cells derived from mouse , hamster , and rat pancreas . ^^^
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In contrast to lean and ob / ob mice , leptin did not stimulate lipolysis in adipocytes from db / db mice , which have a mutation in the leptin receptor gene . ^^^
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Transcripts encoding both the long and short isoforms of the leptin receptor were present in human granulosa cells and thecal cells ; however , the short isoforms were expressed at much higher levels . ^^^ In conclusion , this study has demonstrated that the leptin receptor is expressed in the human ovary , that leptin is present in follicular fluid , and that leptin can induce a biological response in ovarian cells . ^^^
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Divergent signaling capacities of the long and short isoforms of the leptin receptor . ^^^
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Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus . ^^^ The weight reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor ( LR ) in the hypothalamus . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Localization of leptin receptor ( Ob R ) messenger ribonucleic acid in the rodent hindbrain . ^^^ We have investigated whether the leptin receptor gene is expressed in hindbrain regions known to be involved in the processing of satiety and energetic signals of peripheral origin . ^^^ Similar levels of leptin receptor gene expression were present in the hindbrain of lean and obese ( ob / ob ) mice . ^^^ The leptin receptor gene was expressed comparatively weakly in the nucleus of the solitary tract of the rat and was not detectable in the lateral parabrachial nucleus . ^^^ A number of rodent hindbrain sites expressing the leptin receptor gene are activated by circulating leptin and may form a monitoring / signaling pathway to complement more direct hypothalamic interactions . . ^^^
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Upregulation of leptin receptor gene expression in the anterior pituitary of human growth hormone releasing hormone transgenic mice . ^^^ The recently cloned leptin receptor ( OB R ) is expressed in many tissues , including the anterior pituitary . ^^^
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Fasting increases leptin receptor mRNA expression in lean but not obese ( ob / ob ) mouse brain . ^^^ Using a non radioactive in situ hybridization detection method , we found that fasting up regulated leptin receptor mRNA expression in the brain of C 57 Bl / 6 lean ( + / + ) but not obese ( ob / ob ) mice . ^^^ After the lean mice were fasted for 24 h , increased leptin receptor mRNA expression was found in the arcuate and ventromedial hypothalamic nuclei , medial habenular nucleus and dentate gyrus of hippocampal formation . ^^^ There was only a minor increase in mRNA expression of leptin receptor in the hippocampus proper while the piriform cortex remained unchanged . ^^^ However , after the obese mice were fasted for 24 h , no detectable changes of leptin receptor mRNA expression could be found . ^^^
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We overexpressed the wild type full length `` b ' ' isoform of the leptin receptor ( OB Rb ) in ZDF islets by perfusing ZDF pancreata with recombinant adenovirus containing the cDNA encoding OB Rb . ^^^
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The obese Zucker fa / fa rats bear a mutation in the leptin receptor gene ( OB R ) and are leptin resistant . ^^^
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Quantification of the full length leptin receptor ( OB Rb ) in human brown and white adipose tissue . ^^^ Levels of expression of the leptin receptor ( OB R ) splice variants have been studied in human omental white and perirenal brown adipose tissues by reverse transcription PCR . ^^^
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Localization of leptin binding domain in the leptin receptor . ^^^ The leptin receptor is a member of the class 1 cytokine receptor family and is involved in the control of appetite and body weight . ^^^ The predicted amino acid sequence of the extracellular region of the cloned leptin receptor differs from that of many other cytokine receptors in that it contains two homologous segments representing potential ligand binding sites . ^^^ After the analysis of various deletion and substitution mutants of the leptin receptor , we found that the first potential binding motif is not required for leptin binding and receptor activation , whereas modification of the second potential binding motif can lead to inactive receptor mutants . ^^^ Coexpression of the active isoform of leptin receptor ( OB Rb ) with an inactive mutant lacking high affinity leptin binding site led to suppression of the activity mediated by OB Rb , suggesting that the leptin receptor may exist as a multimeric complex in the absence of leptin . . ^^^
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In addition , all forms of leptin receptor are known to be defective in fa / fa rats . ^^^
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Differential expression and regulation of leptin receptor isoforms in the rat brain : effects of fasting and oestrogen . ^^^ Different isoforms of the leptin receptor ( leptin R ) exist , including a long isoform ( leptin RL ) with signalling capacity and short isoforms ( leptin RS ) with unknown function . ^^^
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The biological activity of both fractions resulting from proper renaturation was further evidenced by their ability to stimulate DNA synthesis in leptin sensitive BAF / 3 cells transfected with a long form of human leptin receptor construct . . ^^^
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Three isoforms of the leptin receptor , OB Ra , b , and f , were detected by RT PCR analysis of total RNA from rat islets . ^^^ The recently discovered adipose cell specific hormone called leptin decreases food intake and increases energy expenditure in rodents through a pathway involving hypothalamic leptin receptors , OB R . ^^^ Finally , leptin was totally inefficient in islets isolated from obese fa / fa rats , which bear a mutation in OB R . ^^^ These results suggest that , in normal rodent islets , leptin specifically inhibits IBMX potentiated glucose induced insulin secretion , through a direct effect involving at least one of the three isoforms of OB R expressed in islets . . ^^^
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Possible candidate genes include LEPR ( leptin receptor ) , at 1p31 , and ASIP ( agouti signaling protein ) , at 20q11 . 2 . . ^^^
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Leptin receptor immunoreactivity , revealed by an antiserum that recognizes all leptin receptor isoforms , was demonstrated in choline acetyltransferase ( ChAT ) containing neurones of the dorsal motor nucleus of the vagus nerve ( DMX ) . ^^^
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Since leptin receptor expression has been found in several tissues including small intestine , a possible role of leptin in sugar absorption by the intestine was investigated . ^^^
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Leptin and the leptin receptor genes have been identified as the site of mutations in the peripheral adipocyte hormone pathway responsible for obesity in the ob / ob mouse ( Zhang et al . , 1994 ) and the db / db mouse ( Chen et al . , 1996 ) . ^^^ In obese humans , ob / ob like mutations in leptin are rare but confirm a role for leptin ( Montague et al . , 1997 ) , and db / db like mutations in the leptin receptor have not been found ( Considine et al . , 1996a ) ; however , the increased understanding of the molecular basis for obesity has generated tremendous interest among scientists and patients alike . ^^^
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Recent studies demonstrated that leptin receptor mRNA is expressed in pancreatic islets of rodents and that leptin at relatively high doses inhibits glucose induced insulin secretion from rat islets . ^^^
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Localization of leptin receptor immunoreactivity in the lean and obese Zucker rat brain . ^^^ A gene defect in the Zucker obese rat causes an amino acid substitution in the leptin receptor and reduced leptin binding at the cell surface . ^^^ An antiserum to a portion of the mouse leptin receptor ( AA 877 894 ) located within the intracellular domain was used to label Zucker lean ( Fa / ? ) and obese ( fa / fa ) rat brain sections . ^^^
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Like other growth factors and cytokines , leptin binding proteins including soluble leptin receptor are present in human serum . ^^^ In the presence of normal leptin receptor ( functional long form , i . e . , OB Rb ) mRNA expression and in the absence of leptin receptor gene mutations , it is logical to assume defective leptin signaling and / or impaired affector system ( s ) are the likely causes of leptin resistance in . ^^^
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Immunohistochemical localization of leptin receptor in the rat brain . ^^^ The distribution of leptin receptor in the rat brain was determined by immunocytochemistry and Western blotting . ^^^ Strong leptin receptor immunoreactivity was detected in the arcuate , paraventricular and ventromedial nuclei of the hypothalamus , and lateral hypothalamic area . ^^^
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A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction . ^^^ Leptin acts through the leptin receptor , a single transmembrane domain receptor of the cytokine receptor family . ^^^ In rodents , homozygous mutations in genes encoding leptin or the leptin receptor cause early onset morbid obesity , hyperphagia and reduced energy expenditure . ^^^ Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains . ^^^
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Leptin receptor gene in a large cohort of massively obese subjects : no indication of the fa / fa rat mutation . ^^^ The massive obesity caused in rodents by the disruption of the leptin receptor signal through genetic defects at the level of either leptin ( OB ) or leptin receptor ( OB R ) has raised the question of the relevance of these genes to morbid obesity in humans . ^^^ In this study , we screened a large population of massively obese subjects for the presence of a leptin receptor mutation homologous to that of fa / fa rats , a single base substitution changing glutamine 269 , a highly conserved glutamine found at position 270 in the human sequence . ^^^
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Absence of soluble leptin receptor in plasma from dbPas / dbPas and other db / db mice . ^^^ The leptin receptor ( Ob R ) is alternatively spliced into at least five different RNAs designated Ob R ( a e ) . ^^^ The presence of an approximately 120 kDa soluble leptin receptor in mouse plasma was confirmed by precipitation with leptin Sepharose beads followed by immunobloting with anti leptin receptor antibodies . ^^^ The soluble leptin receptor is larger than that predicted by the primary sequence . ^^^
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The assignment of the leptin receptor gene ( LEPR ) to pig chromosome 6q32 35 excluded LEPR as a candidate gene for a QTL on pig chromosome 4 with a major effect on fatness . . ^^^
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Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting . ^^^ The responsiveness of the hypothalamus to the inhibitory effects of leptin on food intake and body weight is influenced by multiple factors , including deficiency of either leptin or leptin receptors ( Ob R ) . ^^^ To investigate whether altered expression of Ob R in the hypothalamus could potentially contribute to altered leptin sensitivity , we performed in situ hybridization with riboprobes that detected either mRNAs encoding both the long ( Ob Rb ) and short ( Ob Ra ) splice variants or mRNA encoding only Ob Rb . ^^^
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The elevated plasma leptin concentration in the Lep ( rdb ) / + mice suggests that LEPR may mediate autocrine suppression of Lep expression . ^^^ In an effort to understand the genetics of human obesity , we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene defective ( Lep ( ob ) / Lep ( ob ) ) and leptin receptor gene defective ( Lep ( rdb ) / Lep ( rdb ) ) mouse . ^^^ These results raise the possibility that human mutations that have even subtle effects on the leptin / leptin receptor system in either the homozygous or heterozygous state may have significant effects on adiposity . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin is an adipocyte derived cytokine that regulates food intake and body weight via interaction with its Ob receptor ( ObR ) . ^^^ Serum leptin levels are chronically elevated in obese humans , suggesting that obesity may be associated with leptin resistance and the inability to generate an adequate ObR response . ^^^ Our findings indicate that SHP 2 is a negative regulator of STAT 3 mediated gene induction after activation of ObR and raise the possibility that blocking the interaction of SHP 2 with ObR could overcome leptin resistance by boosting leptin ' s weight reducing effects in obese individuals . . ^^^ Enhancing leptin response by preventing SH 2 containing phosphatase 2 interaction with Ob receptor . ^^^
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Leptin receptor is product of db genes . ^^^ Leptin receptor gene is expressed in abundant degree in ovary , uterus , testes , less in hypothalamus , hypophysis , and little in kidney . ^^^
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Specific [ 125I ] leptin receptor binding sites have been identified in choroid plexus ( CP ) , but have eluded regional localization within the brain parenchyma . ^^^
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A locus contributing to plasma leptin levels ( lod score 5 . 3 ) but not obesity was identified on chromosome 4 , near the leptin receptor gene . ^^^
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Leptin receptor signal transduction : OBRa and OBRb of fa type . ^^^ We report herein the characterization of activities of signal transduction for three types of leptin receptors ( OBRs ) from rats , the OBRa , OBRb , and OBRb with fa mutation ( OBRb fa ) , by measurement of the levels of tyrosine phosphorylation of STAT 3 ( signal transducers and activators of transcription 3 ) and MAPK ( mitogen activated protein kinase ) , which are induced by leptin stimulation of CHO cells stably expressing the OBR ( CHO OBRb , CHO OBRa , or CHO OBRb fa cells ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Distributions of leptin receptor mRNA isoforms in the rat brain . ^^^ We have systematically examined distributions of mRNA of leptin receptor isoforms in the rat brain by using a probe specific for the long form and a probe recognizing all known forms of the leptin receptor . ^^^ A probe recognizing all known forms of the leptin receptor hybridized to all of these sites within the brain . ^^^ The localization of leptin receptor mRNA in extrahypothalamic sites in the thalamus and cerebellum suggests that leptin may act on specific sensory and motor systems . ^^^
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Isoforms of the leptin receptor , members of the interleukin 6 cytokine family of receptors , are found in multiple tissues , including the brain . ^^^
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We also assayed for changes in mRNA levels of IL 1 system components , TNF alpha , TGF beta 1 , glycoprotein 130 ( gp 130 ) , leptin receptor ( OB R ) , pro opiomelanocortin ( POMC ) , neuropeptide Y ( NPY ) , glucocorticoid receptor ( GR ) , and CRF receptor ( CRF R ) in selected brain regions . ^^^
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These include the hormone leptin , the short and long forms of the leptin receptor , uncoupling proteins , agouti protein , melanocortin receptor isoforms , melanin concentrating hormone , and the proteins responsible for tub and fat , two monogenic mouse models of obesity . ^^^
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CNTF exerts its multiple effects through a receptor complex whose sequence , localization in hypothalamic nuclei and mode of signal transduction share remarkable similarities with the leptin receptor . ^^^
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Leptin and the leptin receptor are key players in the regulation of body weight . ^^^ In an attempt to dissect the molecular mechanism of the Zucker fatty rat leptin receptor mutation ( Gln 269 > Pro ) we analyzed the effects of this mutation on leptin receptor signaling and expression in three different expression systems : 1 ) 32D cells expressing leptin / erythropoietin receptor chimeras , 2 ) COS 7 cells expressing a leptin receptor short form , and 3 ) 293 cells expressing soluble receptor forms . ^^^ Our results suggest that the obese phenotype resulting from the Gln 269 > Pro mutation in the leptin receptor of the Zucker fatty rat may be due not only to a reduced cell surface expression of this form of the leptin receptor , but also to a post leptin binding malfunction of the receptor that interferes with subsequent signal transduction . . ^^^
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A leptin dependent increase of SOCS 3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form . ^^^
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The predicted amino acid sequence of leptin from the Syrian hamster was over 90 % homologous with Djungarian hamster and mouse sequences , and the leptin receptor gene ( OB R ) , and specifically the long intracellular splice variant , OB Rb , was expressed in the same forebrain and hypothalamic regions that have been described in laboratory mice and rats , including hypothalamic arcuate , dorsomedial , and ventromedial nuclei . ^^^
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Leptin receptor isoforms expressed in human adipose tissue . ^^^ This has been considered the major role of leptin , but leptin receptor isoforms are expressed not only in the brain but also in most other tissues in humans and rodents : heart , placenta , lung , liver , muscle , kidney , pancreas , spleen , thymus , prostate , testes , ovary , small intestine , and colon . ^^^ Four splice variants of the leptin receptor have been identified in humans : the long isoform huOb R and the shorter isoforms B219 . 1 to B219 . 3 . ^^^ Here , we report the identification by reverse transcriptase polymerase chain reaction ( RT PCR ) of three leptin receptor isoforms coexpressed in human visceral adipose tissue : the long isoform huOb R and the short isoforms huB219 . 1 and huB219 . 3 . ^^^
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Expression of peroxisome proliferator activated receptor alpha ( PPARalpha ) and enzymes of fatty acid ( FA ) oxidation is markedly reduced in the fat laden , dysfunctional islets of obese , prediabetic Zucker diabetic fatty ( fa / fa ) rats with mutated leptin receptors ( OB R ) . ^^^
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The leptin receptor gene is expressed in a wide range of tissues , and several splice variants are evident . ^^^
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Expression of leptin receptor isoforms in rat brain microvessels . ^^^ High expression of a short form leptin receptor has been reported in the choroid plexus . ^^^ However , whether one or more of the known leptin receptor isoforms is expressed in brain capillaries is unknown . ^^^ To identify and quantitate leptin receptor isoforms in rat brain microvessels , we applied quantitative RT PCR to RNA from purified rat brain microvessels in parallel with in situ hybridization . ^^^ The results show that the amount of short form leptin receptor messenger RNA ( mRNA ) in brain microvessels is extremely high , exceeding that in choroid plexus . ^^^
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Leptin completely blocked FA induced Bcl 2 suppression in normal islets but had no effect on islets from fa / fa rats , which are unresponsive to leptin because of a mutation in their leptin receptors ( OB R ) . ^^^ However , when wild type OB R is overexpressed in fa / fa islets , leptin completely prevented FA induced Bcl 2 suppression and DNA fragmentation . . ^^^
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Leptin Receptor ] . ^^^ Its effects are mediated by interactions with the leptin receptor ( Ob R ) that is alternatively spliced to encode at least five isoforms ( a e ) , which are distributed in a wide range of tissues including the hypothalamus . ^^^
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Genetic analysis of F 2 males from both cross directions identified an NON derived diabetogenic locus , Nidd 1 , on chromosome ( Chr ) 4 near the leptin receptor . ^^^
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A common pentanucleotide polymorphism of the 3 ' untranslated part of the leptin receptor gene generates a putative stem loop motif in the mRNA and is associated with serum insulin levels in obese individuals . ^^^ OBJECTIVE : To find out whether genetic alterations of the leptin receptor gene underlie human forms of obesity . ^^^ DESIGN : Among 249 morbidly obese adults ( body mass index , BMI > or = 40 kg / m2 ) , we screened 30 patients with the highest serum leptin levels for alterations of their leptin receptor gene by single strand conformation polymorphism ( SSCP ) technique . ^^^ RESULTS : We were able to detect a pentanucleotide insertion ( CTTTA ) in the 3 ' untranslated region of the leptin receptor gene . ^^^ CONCLUSIONS : We were able to confirm the presence of a frequent insertion / deletion polymorphism close to the 3 ' end of the leptin receptor gene . ^^^
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To obtain in vivo evidence that leptin may act peripherally as well as centrally , we compared the effect of adenovirally induced hyperleptinemia on food intake , body weight , and islet fat content in ventromedial hypothalamic lesioned ( VMHL ) rats , sham lesioned ( SL ) controls , and Zucker Diabetic Fatty ( ZDF ) rats in which the leptin receptor is mutated . ^^^
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The objective of this project was to identify sequence tagged sites ( STSs ) in the Asian and the African elephant for the following genes : melatonin receptor 1a ( MTNR1A ) , retinoic acid receptor beta ( RARB ) , and leptin receptor ( LEPR ) . ^^^
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Db / db mutant mice show a similar phenotype , here the defect lies in the block of leptin receptor downstream signalling . ^^^ Human obesity might be connected to a defect of leptin receptor or to its altered signal transduction . ^^^
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Expression of the leptin receptor in human leukaemic blast cells . ^^^ The leptin receptor is a member of the cytokine receptor superfamily , and is expressed in CD 34 haemopoietic stem cells . ^^^ We examined expression of the leptin receptor in fresh human leukaemia cells . ^^^ Northern blot analysis showed the leptin receptor was expressed in leukaemic cells from patients with acute myeloblastic leukaemia , acute lymphoblastic leukaemia and chronic myeloid leukaemia ( CML ) . ^^^ The expression of leptin receptor decreased during in vitro differentiation of leukaemic blast cells . ^^^
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Functional properties of leptin receptor isoforms containing the gln > pro extracellular domain mutation of the fatty rat . ^^^ Mutations of the leptin receptor have been found to cause obesity in rodents . ^^^ The fa mutation that is responsible for obesity in Zucker rats is a missense mutation ( 269 gln > pro ) in the extracellular domain of the leptin receptor . ^^^ We have characterized the effects of this mutation on the two major isoforms of the leptin receptor , Ob Rb and Ob Ra , by studying cell surface expression , leptin binding affinity , signaling capacity , and receptor mediated internalization and degradation of leptin in transfected mammalian cell lines . ^^^
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Leptin receptor density was doubled in the hypothalamus of tumor bearing rats , while binding affinity was decreased by 50 % . ^^^
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The hypothalamic expression patterns of corticotropin releasing hormone ( CRH ) and the long form leptin receptor ( OB Rb ) were not significantly altered in the mutant mice . ^^^
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Monkey leptin receptor mRNA : sequence , tissue distribution , and mRNA expression in the adipose tissue of normal , hyperinsulinemic , and type 2 diabetic rhesus monkeys . ^^^ OBJECTIVE : We have cloned the rhesus monkey leptin receptor and examined its mRNA expression levels in the adipose tissue of monkeys to investigate the regulation of gene expression of the leptin receptor . ^^^ RESEARCH METHODS AND PROCEDURES : Monkey leptin receptor cDNA was cloned by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ Tissue distribution of monkey leptin receptor was examined by Northern blot analysis and RT PCR . ^^^ The mRNA levels of monkey leptin receptor in adipose tissue of normal ( n=10 ) , hyperinsulinemic obese ( n=8 ) , and type 2 diabetic monkeys ( n=8 ) were measured by quantitative RT PCR . ^^^
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The OE induced changes in hypothalamic CRH require a fully functional leptinergic pathway , because it is not observed in Zucker fa / fa rats lacking a working leptin receptor . ^^^
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Leptin receptor immunoreactivity is associated with the Golgi apparatus of hypothalamic neurons and glial cells . ^^^ The present study reports the predominant localization of leptin receptor immunoreactivity in the cis and trans cisternae of the Golgi apparatus in hypothalamic neuronal and glial cells . ^^^ In these hypothalamic cells , translocation of leptin receptor immunoreactivity from the Golgi apparatus to the perikaryal membrane , nucleus or to the cytoplasm was not apparent after manipulation of the metabolic state either by fasting or suppression of the thyroid axis . ^^^ On the other hand , leptin receptor immunoreactivity was associated with the perikaryal membrane of neurones in other parts of the central nervous system , including the dentate gyrus and the cingulate cortex . ^^^
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We now describe leptin receptor expression and in vivo signaling in discrete regions of the mouse gastrointestinal tract . ^^^ Expression of the functional isoform leptin receptor ( OB Rb ) is restricted to the jejunum and is readily detected by RT PCR in isolated enterocytes from this site . ^^^
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Up regulation of blood brain barrier short form leptin receptor gene products in rats fed a high fat diet . ^^^ Leptin may gain access to the brain via receptor mediated transport through the blood brain barrier ( BBB ) , and the BBB leptin receptor ( OBR ) may regulate the availability of circulating leptin to brain cells . ^^^ This investigation demonstrates ( a ) the OBRa is the principal leptin receptor expressed at the BBB and ( b ) this BBB OBR isoform is up regulated by a high fat diet . . ^^^
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These effects of leptin in adrenal cells are likely mediated by the long isoform of the leptin receptor ( OB R ) , because its transcript was found to be expressed in the adrenal tissue and leptin had no inhibitory effect in adrenal glands obtained from db / db mice . ^^^
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Because ZDF rats are homozygous for a mutation in their leptin receptor ( OB R ) gene and are therefore leptin insensitive , we expressed the wild type OB R gene in diabetic islets by infusing a recombinant adenovirus ( AdCMV OB Rb ) to determine whether this reversed the abnormalities . ^^^ Leptin induced a rise in phosphorylated STAT 3 , indicating that the transferred wild type OB R was functional . ^^^
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Human leptin receptor . ^^^ The leptin receptor ( OB R ) is a member of the class 1 cytokine receptor family and mediates the weight regulatory effects of its ligand through interaction with cytoplasmic kinases . ^^^ The extracellular domain of human leptin receptor was expressed in and purified from Chinese hamster ovary cells and was found to contain extensive N glycosylation ( approximately 36 % of the total protein ) . ^^^ The determined disulfide motif of the soluble leptin receptor contained several distinct cystine knots as well as 10 free cysteines . ^^^
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To elucidate the pathophysiologic significance of UCP 3 and UCP 2 in the effect of TZDs on glucose metabolism and energy expenditure , we examined their basal mRNA levels in the WAT , brown adipose tissue ( BAT ) , and skeletal muscle from Wistar fatty rats , a rat model of NIDDM and obesity with leptin receptor defect , and investigated expression of the genes encoding UCP 3 and UCP 2 in Wistar fatty rats and in Wistar lean rats with 2 week oral administration of 3 mg 10 kg ( 1 ) 10 day ( 1 ) pioglitazone , a TZD derivative . ^^^ These results clearly demonstrate that UCP 3 gene expression is upregulated by TZDs in the WAT and BAT in Wistar fatty rats , an obese model with leptin receptor defect , and that adipose UCP 3 gene expression is increased in response to TZDs in vitro . ^^^
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Localization of leptin receptor splice variants in mouse peripheral tissues by immunohistochemistry . ^^^
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It remains unclear how signaling is propagated downstream from the leptin receptor to STAT 3 , but this may involve novel signaling intermediates . . ^^^
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To identify targets for leptin ' s action , we used in situ hybridization and computerized imaging to map leptin receptor ( Ob R ) messenger RNA ( mRNA ) distribution . ^^^
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HpaII and RsaI PCR RFLPs within an intron of the porcine leptin receptor gene ( LEPR ) and its linkage mapping . ^^^
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Association of leptin receptor ( OB Rb ) , NPY and GLP 1 gene expression in the ovine and murine brainstem . ^^^ Since some leptin signaling is integrated in the rodent brainstem , and leptin modulates neuropeptidergic activity , we now describe leptin receptor ( long splice variant , OB Rb ) , neuropeptide Y ( NPY ) and glucagon like peptide 1 ( GLP 1 ) gene expression in the ovine brainstem . ^^^ Leptin receptor mRNA was localized to the spinal trigeminal tract and nucleus , nucleus of the solitary tract ( NTS ) , area postrema and dorsal motor nucleus of the vagus . ^^^ However , in an extension of earlier work , co expression studies in the murine brainstem revealed only a small number of neurons that expressed both NPY and leptin receptor mRNA , despite the widespread and abundant expression of the former . ^^^
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Several isoforms of the leptin receptor are expressed in pancreatic beta cells . ^^^
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We describe a rapid , sensitive and quantitative in vitro assay for leptin using HEK 293 cells stably co transfected with the leptin receptor Ob Rb isoform and a STAT inducible promoter regulating the firefly luciferase cDNA . ^^^ Furthermore , we demonstrate that a leptin derived peptide , leptin fragment 22 56 , previously shown to be capable of reducing feed intake following ICV injection does not act directly through the leptin receptor . . ^^^
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Intact leptin receptor is selectively expressed in human fetal pituitary and pituitary adenomas and signals human fetal pituitary growth hormone secretion . ^^^ The intact leptin receptor ( OB R ) , a single membrane spanning peptide containing an approximately 300 amino acid intracellular domain , is highly expressed in the hypothalamus , whereas shorter OB R isoforms with truncated cytoplasmic regions resulting from alternative splicing have also been identified . ^^^ Thus , pituitary adenomas appear to revert to a fetal phenotype of leptin receptor expression . . ^^^
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The presence of 170 kDa endothelial leptin receptor ( Ob R ) was assessed in HUVECs by Western blot analysis . ^^^ These results indicate that leptin , via activation of the endothelial Ob R , generates a growth signal involving a tyrosine kinase dependent intracellular pathway and promotes angiogenic processes . ^^^
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These sorting nexins also associated with the long isoform of the leptin receptor but not with the short and medium isoforms . ^^^
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Mouse placental cells secrete soluble leptin receptor ( sOB R ) : cAMP inhibits sOB R production . ^^^ Addition of leptin to the medium did not affect expression of OB R mRNA . ^^^
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Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term . ^^^ OBJECTIVE : To demonstrate the expression of messenger RNA ( mRNA ) transcripts for placental leptin and leptin receptor in early gestation and at term , to quantitate transcriptional changes relative to stage of gestation , to localize transcripts within specific placental cell types , and to determine if transcripts also are expressed in cultured cells . ^^^ METHODS : Expression of leptin and leptin receptor was assessed by reverse transcriptase polymerase chain reaction , and leptin quantitated against a leptin mRNA competitor ( MIMIC ) , in human placental villous tissue collected at term cesarean deliveries and earlier during gestation ( 7 14 weeks ) upon elective terminations . ^^^ RESULTS : Placental leptin and leptin receptor transcripts were identified in early ( n = 6 ) and late ( n = 5 ) gestation . ^^^ Leptin and leptin receptor transcripts were localized in trophoblast by in situ hybridization and were expressed in culture . ^^^
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Hyperleptinemia and leptin receptor variant Asp600Asn in the obese , hyperinsulinemic KK mouse strain . ^^^ The cDNA sequence of leptin is normal in KK mice , whereas three nucleotide polymorphisms were found in the cDNA of the leptin receptor , one of them resulting in exchange of an aspartate residue for asparagine ( Asp600Asn ) in a highly conserved part of the second extracellular cytokine receptor homology module . ^^^ In female ( but not male ) F 2 mice of a C57BL / 6JxKK intercross , the weight of gonadal , retroperitoneal and mesenteric adipose tissue was positively correlated with the number of alleles inherited from the KK parental strain at a microsatellite marker ( D4Mit175 ) which maps close ( 0 . 7 centimorgan proximal ) to the leptin receptor gene . ^^^ It is suggested that the Asp600Asn leptin receptor variant contributes to the obesity syndrome in KK female mice , but that its contribution is only a part of the multigenic syndrome . . ^^^
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Functional full length leptin receptor messenger ribonucleic acid and all human isoforms Ob219 . 1 3 were demonstrated by RT PCR in both cortical and medullary tissue . ^^^ Immunohistochemical staining of leptin receptor protein , however , demonstrated a strong signal only in the adrenal cortex , whereas there was weak positive staining in the medulla . ^^^ In conclusion , this is the first report identifying functional leptin receptor in human adrenal tissue and showing a differential action of leptin on human adrenocortical and chromaffin hormone production . ^^^ Expression of Ob receptor in normal human adrenals : differential regulation of adrenocortical and adrenomedullary function by leptin . ^^^
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Obese ( Lepr ( fa ) / Lepr ( fa ) ) Zucker rats have a missense mutation in the leptin receptor gene . ^^^ One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation . ^^^
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The leptin gene codes for a cytokine secreted by fat cells that binds to the leptin receptor ( Lep R ) , which exerts some of its biological functions by expression in the brain . ^^^ Transmission disequilibrium and sequence variants at the leptin receptor gene in extremely obese German children and adolescents . ^^^
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The leptin receptor has at least five splice variants ; the long form of the receptor is primarily expressed in the hypothalamus and is thought to be the predominant signaling isoform . ^^^ Mutations in the leptin or leptin receptor genes results in morbid obesity , infertility , and insulin resistance in rodents and humans . ^^^
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Phenotypic consequences of a nonsense mutation in the leptin receptor gene ( fak ) in obese spontaneously hypertensive Koletsky rats ( SHROB ) . ^^^ The genetically obese Koletsky rat ( SHROB , fak ) has a novel point mutation of the leptin receptor at amino acid +763 , resulting in a premature stop codon in the leptin receptor extracellular domain . ^^^ This implies that all leptin receptor isoforms should be absent in this model . ^^^ We examined the phenotypic consequences of this mutation on leptin and leptin receptor mRNA in hypothalamus and peripheral tissues from SHROB and their lean SHR littermates . ^^^ Leptin directly suppressed insulin mediated glucose transport by 50 % in skeletal muscle from SHR but not in obese SHROB rats lacking all forms of the leptin receptor . ^^^
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Due to hypothalamic leptin receptor mutations or dysfunctions , leptin can not exert its eflects : NPY levels ( possibly those of other neuropeptides ) remain elevated , maintaining excess storage , insulin as well as leptin resistance . . ^^^
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Ultrastructural immunolocalization of leptin receptor in mouse brain . ^^^ Antibodies directed to amino acids 877 894 ( M 18 ) and 32 51 ( K 20 ) were used to localize leptin receptor by immunocytochemistry in mouse brain . ^^^
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Leptin is an adipose tissue derived hormone that regulates body weight via interactions with hypothalamic neuronal circuitries expressing specific leptin receptors ( Ob R ) . ^^^ The results provide an anatomical basis for a leptin action mediated by STAT 3 in Ob R containing NPY and POMC neurons of the arcuate nucleus , as well as by Ob R containing neurons of the parvocellular paraventricular nucleus and lateral hypothalamic area . . ^^^
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To address this question , we tested mouse strains that were defective either in leptin gene ( ob / ob ) or in functional leptin receptor gene ( db / db ) , and made use of a receptor antagonist of leptin . ^^^
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DESIGN AND METHODS : A polygenic obese animal model , the New Zealand obese mouse ( NZO ) and its age matched control , was used to assess the hypothalamic mRNA expression of NPY , the insulin receptor ( IR ) and the leptin receptor ( Ob Rb ) , by semiquantitative polymerase chain reaction . ^^^
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In addition , refolded leptin is characterized by radioimmunoassay ( RIA ) and activation of the leptin receptor in a cell based assay . ^^^
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The biological activity of both fractions , resulting from proper renaturation , was further evidenced by their ability to stimulate proliferation of leptin sensitive BAF / 3 cells transfected with a long form of human leptin receptor construct and by lowering the food intake of starved chicken following intravenous or intraperitoneal injections . . ^^^
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These results imply that leptin stimulated release of a circulating growth factor , possibly through activation of the long form leptin receptor , in ob / ob partners of db / db mice . . ^^^
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It appears that either mouse leptin does not bind to the chicken leptin receptor or in the chicken brain the leptin receptor may be absent . . ^^^
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Although one of the sites of action of leptin is likely to be the hypothalamus , since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei , the mechanisms by which leptin regulates GH secretion are not yet known . ^^^
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Double label in situ hybridization studies in the brain of the mouse , rat , and monkey have revealed that hypothalamic neurons expressing proopiomelanocortin and neuropeptide Y coexpress the leptin receptor , whereas no evidence has been adduced that GnRH neurons express this receptor . ^^^
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Mutations reducing the functional activity of leptin , the leptin receptor , alpha melanocyte stimulating hormones ( alpha MSH ) and the melanocortin 4 receptor ( Mc4r ) all lead to obesity in mammals . ^^^
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A leptin receptor is related to gp 130 , a signal transducer among interleukin ( IL ) 6 subfamily receptors ; gp 130 and related molecules may be an interface for feeding control in health and disease . ^^^
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Free leptin , bound leptin , and soluble leptin receptor in normal and diabetic pregnancies . ^^^ We measured serum levels of free leptin , bound leptin , and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum , and analyzed the data using hierarchical statistical models . ^^^ Diabetic subjects , however , had significantly higher soluble leptin receptor levels at all stages ( P < < 0 . 001 ) , which rose further in the third trimester from 3742 + / 268 ( mean + / SEM ) to 4134 + / 239 pmol / L , whereas in the normal group there was a fall from 3149 + / 169 to 2712 + / 123 ( P = 0 . 05 ) . ^^^ There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only . ^^^ We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin dependent diabetic subjects either during pregnancy or postpartum , but female insulin dependent diabetic subjects have significantly higher soluble leptin receptor levels . ^^^
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In addition , hypocretin containing neurons also express leptin receptor immunoreactivity . ^^^
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Only a few obese humans have been identified with mutations in the leptin gene or in the leptin receptor ; however , most cases of obesity in humans are associated with high leptin levels . ^^^
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BACKGROUND : Leptin is known to be cleared by the kidney , a tissue with substantial leptin receptor mRNA expression ; however , lung , liver , and muscle tissues also express leptin receptor messenger RNA and it is not known whether these tissues also clear leptin from the circulation . ^^^
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The long terminal repeat of an endogenous retrovirus induces alternative splicing and encodes an additional carboxy terminal sequence in the human leptin receptor . ^^^ This type of regulatory pathway is illustrated by the alternative splicing in the human leptin receptor ( OBR ) . ^^^ The human leptin receptor is involved in the control of important biological processes including energy expenditure , production of sex hormones , and activation of hemopoietic cells . ^^^ OBRa and OBRb are the two major , alternatively spliced forms of the leptin receptor , called the `` short form ' ' and the `` long form , ' ' respectively . ^^^
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Expression of leptin receptor in lung : leptin as a growth factor . ^^^ The present studies were undertaken to investigate the function of the leptin receptor in mouse and human lungs . ^^^ Reverse transcription polymerase chain reaction ( RT PCR ) study demonstrated the existence of a long form , OB Rb type leptin receptor in both human lung tissue and lung squamous cell line ( SQ 5 ) . ^^^ In conclusion , leptin ( OB Rb ) receptors exist in human lung tissue and leptin may have stimulatory effects on the proliferation of cells of a human cell line and mouse tracheal epithelial cells through its specific leptin receptor . . ^^^
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Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta cells and an inhibition of insulin secretion by leptin via activation of ATP sensitive potassium channels . ^^^
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Leptin receptor long form splice variant protein expression in neuron cell bodies of the brain and co localization with neuropeptide Y mRNA in the arcuate nucleus . ^^^ Reduced leptin ( Ob protein ) signaling is proposed to be a stimulus for the activation of neuropeptide Y ( NPY ) gene activity and increased expression of mRNA for the long form of the leptin receptor ( Ob Rb ) in the hypothalamic arcuate nucleus . ^^^ This antibody specifically recognizes the cytoplasmic tail of Ob Rb and does not react with shorter leptin receptor variants . ^^^
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These neuropeptide Y neurons express the Ob Rb leptin receptor and are overactive in the fatty ( fa / fa ) Zucker rat . ^^^ The fa mutation affects the extracellular domain of the leptin receptor , but its impact on leptin action and neuropeptide Y neuronal activity is not fully known . ^^^
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Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes : proliferative and anti apoptotic activities . ^^^ Therefore , we studied the expression of the leptin receptor , OB R , in normal myeloid precursors , human leukemia cell lines , and primary leukemic cells using reverse transcriptase polymerase chain reaction . ^^^ Results confirm the reported expression of leptin receptor in normal CD 34 ( + ) cells and demonstrate the frequent expression of leptin receptors in AML blasts . ^^^
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In order to more fully characterize the regulation of CYP2E1 and CYP4A in obesity and obesity related ( type 2 ) diabetes , we analyzed the hepatic expression of CYP2E1 and CYP4A in ob / ob mice which are leptin deficient , and fa / fa Zucker rats which have defective leptin receptor function . ^^^ Further , they implicate leptin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation . . ^^^
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Expression of leptin receptor mRNA and the long form splice variant in human anterior pituitary and pituitary adenoma . ^^^ Expression of leptin receptor ( OB R ) mRNA was detected in the human anterior pituitary as well as in ACTH secreting and nonsecreting pituitary adenomas by RT PCR with primers recognizing all receptor splice variants . ^^^ Primers specific to the long splice variant of the leptin receptor ( OB Rb ) , containing the putative intracellular signalling domain , also revealed a strong expression in normal and adenomatous anterior pituitaries . ^^^
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Tyrosine phosphorylation of STAT 3 by leptin through leptin receptor in mouse metaphase 2 stage oocyte . ^^^ In this report , we studied the expression of leptin receptor and STAT 3 activation by leptin in metaphase 2 stage ( M 2 ) oocytes . ^^^ Reverse transcriptase polymerase chain reaction ( RT PCR ) and immunoblotting showed that mRNA and protein of leptin receptor were expressed in M 2 stage oocyte . ^^^
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RT PCR analysis demonstrated that the long , signaling form of the leptin receptor was expressed in both theca and GC . ^^^
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Expression of a leptin receptor in immortalized gonadotropin releasing hormone secreting neurons . ^^^ Leptin is secreted by adipocytes and regulates food intake and energy balance through the activation of specific receptors ( OB R ) . ^^^
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By RT PCR and Western immunoblot analysis , the hMS 2 12 cells expressed messenger RNA ( mRNA ) and protein for the leptin receptor . ^^^
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In three rare cases of human morbid obesity , the discovery of mutations in the leptin and leptin receptor genes shows that leptin plays a crucial role in the control of weight and several endocrine functions ( particularly reproduction ) . ^^^ Previous searches for mutations in the leptin and leptin receptor genes indicated that these are probably not major genes for common forms of human obesity . ^^^
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Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus . ^^^ To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin , we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor ( Ob Rb ) . ^^^
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The leptin receptor gene is widely expressed , with the several splice variants exhibiting different patterns of expression . ^^^
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Linkages and associations between the leptin receptor ( LEPR ) gene and human body composition in the Qubec Family Study . ^^^ OBJECTIVE : To investigate linkage and association between the leptin receptor ( LEPR ) gene and body composition variables in the Quebec Family Study ( QFS ) . ^^^
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Mutation of the Ob gene , which encodes for leptin , or mutation of the leptin receptor leads to obesity in mice . ^^^ The leptin receptor exists in a long and short form , with the long form primarily expressed in the hypothalamus but also in the lungs and kidneys of the mouse . ^^^
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Dual in situ hybridization reveals that Agrp expressing neurons in the medial portion of the arcuate nucleus constitute a subpopulation different from Pomc expressing neurons , and that a significant proportion of Agrp expressing neurons ( 10 25 % ) coexpresses the leptin receptor , Lepr b . ^^^
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Evidence for ligand independent homo oligomerization of leptin receptor ( OB R ) isoforms : a proposed mechanism permitting productive long form signaling in the presence of excess short form expression . ^^^ The adipocyte secreted hormone leptin ( OB ) and its receptor ( OB R ) are key regulators of mammalian body weight homeostasis . ^^^ These results are discussed with regard to possible mechanisms permitting efficient leptin induced signaling by OB R ( L ) in tissues that co express OB R ( S ) . . ^^^
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Intense immunoreactivity for the leptin receptor was detected in the hypothalamic arcuate nucleus ( ARC ) , ventromedial nucleus ( VMH ) , and lateral hypothalamus ( LH ) by immunohistochemistry . ^^^ These results reveal that leptin inhibits the ARC and LH neurons and stimulates the VMH neurons via the leptin receptor expressed in these cells . . ^^^
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Colocalization of leptin receptor ( OB R ) mRNA and placental lactogen 2 in rat trophoblast cells : gestational profile of OB R mRNA expression in placentae . ^^^ The present study was designed to clarify the cellular localization and expression of leptin receptor ( s ) [ OB R ( s ) ] mRNA including its splice variants and their correlation with the cells which secrete placental hormone , placental lactogen 2 ( PL 2 ) , in rat placentae . ^^^
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Leptin receptor and neuropeptide Y gene expression in the sheep brain . ^^^ To elucidate the function of leptin in sheep we have investigated putative sites of action for leptin in the brain and pituitary gland using both in situ hybridization to detect expression of the signalling form of the leptin receptor ( OB Rb ) and in vitro autoradiography using ( 125I ) leptin to detect sites of specific leptin binding . ^^^
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Genes that have been shown to have a regulatory function in the control of body fat utilization , eating behavior , and / or metabolic rate in rodent models of obesity include leptin ( LEP ) , leptin receptor ( LEPR ) , neuropeptide Y ( NPY ) , NPY Y 1 receptor ( NPYY 1 ) , glucagon like peptide 1 ( GLP 1 ) , GLP 1 receptor ( GLP1R ) , and uncoupling protein 1 ( UCP 1 ) . ^^^
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The arcuate nucleus ( ARC ) mediates the anorexic effects of leptin and expresses the long form ( Ob Rb ) of the leptin receptor . ^^^ These findings suggest that leptin receptor binding in the ARC is upregulated during fasting and that fasting changes the sensitivity of the ARC to leptin . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor immunoreactivity in sympathetic prevertebral ganglion neurons of mouse and rat . ^^^ In the present study , we report the presence of leptin receptor like immunoreactivity in the superior mesenteric and celiac ganglia of mice and rats . ^^^ Ganglion neurons were immunopositive for leptin receptor . ^^^ Confocal microscopy and three dimensional ( 3 D ) reconstruction of ganglion neurons filled with Lucifer yellow and then immunostained for leptin receptor showed that leptin receptor immunoreactivity was intracellular and that it was present on structures encircling the nucleus . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin responsiveness and gene dosage for leptin receptor mutation ( fa ) in newborn rats . ^^^ To determine the degree to which the leptin receptor mutation ( fa ) influences the responsiveness to leptin during the first postnatal week , we injected recombinant leptin ( 600 pmol . g 1 . day 1 sc from day 1 to day 7 ) into wild type ( + / + ) , heterozygous ( + / fa ) , and fatty ( fa / fa ) rat pups . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy , we studied + / + , db / + , and db / + transgenic mice that overexpress the human GLUT 4 gene two to three fold ( db / +TG6 ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Detection of Ob receptor in human adrenal neoplasms and effect of leptin on adrenal cell proliferation . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Functional properties of leptin receptor isoforms : internalization and degradation of leptin and ligand induced receptor downregulation . ^^^ Long ( ObRb ) and short ( ObRa ) leptin receptor isoforms are thought to play essential roles in mediating leptin signaling and the transport and degradation of leptin , respectively . ^^^ We therefore studied these parameters in Chinese hamster ovary ( CHO ) cells stably expressing either ObRa or ObRb isoforms of the leptin receptor . ^^^ Thus , the two leptin receptor isoforms , ObRa and ObRb , mediate leptin internalization by a coated pit dependent mechanism , leptin degradation by a lysosomal pathway , and ligand induced receptor downregulation . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The expression of the long form of the leptin receptor was detected in human platelets . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food anticipatory rhythms to daily feeding schedules . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To further understand the interplay between the central appetite stimulating and peripheral appetite inhibiting signals in the management of daily food intake , we have examined the daily patterns in expression of the hypothalamic neuropeptides and leptin receptor ( R ) and adipocyte leptin gene expression and secretion in freely feeding ( FF ) rats . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We also examined hypothalamic feeding associated components : neuropeptide Y and proopiomelanocortin mRNAs were down regulated , glycoprotein 130 mRNA levels were up regulated , and leptin receptor ( OB R ) mRNA levels were unchanged . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
However , leptin receptor is expressed not only in the central nervous system , but also in other systems such as reproductive and hematopoietic tissues . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin failed to affect food intake or body temperature in obese ( fa / fa ) Zucker rats , which posses a defective leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We have demonstrated previously that pharmacological doses of oestradiol decreased leptin receptor expression in the hypothalamus . ^^^ We therefore analysed leptin receptor expression during the oestrous cycle in the rat , to establish if acute changes in oestradiol affect leptin receptor expression under physiological conditions . ^^^ Total leptin receptor transcript levels were lowest in pro oestrus in the choroid plexus , these changes correspond inversely with levels of circulating oestradiol in the rat 4 day oestrous cycle . ^^^ In contrast full length leptin receptor levels in both arcuate and ventromedial nuclei did not correspond to the levels of total leptin receptor in the same areas of the hypothalamus or serum levels of oestradiol . ^^^ Full length leptin receptor expression in the arcuate nucleus was negatively correlated with neuropeptide Y ( NPY ) expression ( r = 0 . 447 , p < 0 . 05 ) in the same nucleus . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The involvement of leptin in humans revealed by mutations in leptin and leptin receptor genes . ^^^
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The obesity is characterised by hyperinsulinaemia , hyperleptinaemia and hyperplasia of the adipocytes , associated with decreased expression of the OB Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL 1beta , IL 1 receptor type 1 ( IL 1RI ) , IL 1R accessory proteins 1 and 2 ( IL 1R AcP 1 and 2 ) , IL 1 receptor antagonist ( IL 1Ra ) , transforming growth factor beta 1 ( TGF beta 1 ) , glycoprotein 130 ( gp 130 ) , leptin receptor ( OB R ) , neuropeptide Y ( NPY ) and pro opiomelanocortin ( POMC ) in the cerebellum , parieto frontal cortex , hippocampus , hypothalamus , and midbrain of male young ( 3 5 months ) and old ( 24 26 months ) Long Evans rats . ^^^ IL 1R AcP 1 and leptin receptor did not change in any brain region from either young or old rats , suggesting specificity of transcriptional changes . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Genetic studies in inbred obese mice have revealed the ob gene , its product leptin and the leptin receptor as important factors in the regulation of both appetite and energy expenditure . ^^^
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Patients with a homozygous mutation of the leptin receptor resulting in the G > T substitution in the splice donor site of exon 16 were studied in a family of Kabilian origin . ^^^ Exon 16 was not included in the mature mRNA molecule , and a truncated leptin receptor was synthesized which lacked the transmembrane and intracellular domains ; this receptor was unable to transduce the hormonal signal . ^^^
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Leptin is bound in the circulation by a high affinity binding protein , which has been identified as a soluble leptin receptor . ^^^
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Subcellular localization and internalization of the four human leptin receptor isoforms . ^^^ There are four known isoforms of the human leptin receptor ( HLR ) with different C terminal cytoplasmic domains ( designated by the number of unique C terminal amino acids ) . ^^^
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The authors review the potential roles of some important receptors , such as the insulin receptor , beta 3 adrenergic receptor , leptin receptor and peroxisome proliferator activated receptor gamma , in the pathogenesis of human type 2 diabetes . ^^^
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Furthermore , leptin receptor mRNA is expressed in the ovary , suggesting a direct effect on its function . ^^^
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Levels of leptin receptor mRNA and leptin binding are increased in the arcuate nucleus during fasting , principally in NPY / AGRP neurons . ^^^ These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling , and that the arcuate nucleus is an important target of leptin action in the brain . . ^^^
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However , mounting evidence indicates expression of leptin receptor mRNA in various peripheral organs including the adrenal medulla . ^^^ We initially confirmed the expression of leptin receptor ( Ob Rb ) mRNA in cultured porcine adrenal medullary cells . ^^^
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The human growth hormone releasing hormone transgenic mouse as a model of modest obesity : differential changes in leptin receptor ( OBR ) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs . ^^^ We reported previously an increase in leptin receptor ( OBR ) gene expression in the anterior pituitary of human GH releasing hormone ( hGHRH ) transgenic mice . ^^^ In conclusion , 1 ) the modest obesity in hGHRH transgenic mice is associated with increases in leptin synthesis and secretion as well as insulin secretion ; 2 ) GH and / or GHRH as well as leptin and insulin may differentially contribute to the changes in OBR ( L ) gene expression in the anterior pituitary and the hypothalamus ; 3 ) the response of OBR ( L ) gene expression in the hypothalamus to fasting is absent in the modestly obese hGHRH transgenic mice ; and 4 ) somatotrophs are target cells for leptin , and the increase in OBR ( L ) gene expression in the pituitary of hGHRH transgenic mice is due at least in part to the increase in the number of cells expressing OBR ( L ) . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In fact , expression of the long leptin receptor isoform , representing the functional leptin receptor , was specifically downregulated in the hypothalami of obese mice , explaining their inability to generate an adequate response to leptin in the brain . ^^^ The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological , virus induced abnormalities . . ^^^
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Leptin and leptin receptor expression in normal and neoplastic human pituitary : evidence of a regulatory role for leptin on pituitary cell proliferation . ^^^ The leptin receptor consists of a single transmembrane spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms . ^^^ Both long ( OB Rb ) and common ( OB Ra ) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells . ^^^ To test this possibility in human pituitaries , we examined the expression of leptin and OB R in normal and neoplastic pituitaries , and the possible functions of leptin in the pituitary were also analyzed . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor and STAT 3 immunoreactivities in hypocretin / orexin neurones of the lateral hypothalamus . ^^^ To clarify whether leptin may interact with hypocretin / orexin to reduce ingestive behaviour , the presence of leptin receptor immunoreactivity in hypocretin / orexin containing neurones was examined . ^^^ Many leptin receptor and hypocretin / orexin immunoreactive neurones were demonstrated in the lateral hypothalamic area and perifornical region . ^^^ Both direct double labelling and elution restaining methods showed that leptin receptor immunoreactivity was present in the vast majority of hypocretin / orexin containing neurones . ^^^ Galanin neurones were also seen to contain leptin receptor and STAT 3 immunoreactivity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor activation of SH 2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction . ^^^ Leptin binding to the Ob Rb form of the leptin receptor leads to tyrosyl phosphorylation of the cytoplasmic domain of its receptor . ^^^ Tyrosyl phosphorylation of the leptin receptor and signal transducer and activater of transcription 3 ( STAT 3 ) are not affected by phosphorylation of SHP 2 . ^^^ These data suggest that activation of SHP 2 by the leptin receptor results in a decreased phosphorylation of JAK 2 and may act to attenuate leptin signal transduction . ^^^ To identify the components of the leptin signal transduction pathway , an approach was developed in which bacterially expressed phosphorylated fragments of Ob receptor b ( Ob Rb ) were used as affinity agents . ^^^
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Recent studies have shown that the leptin receptor is expressed on a diverse range of hemopoietic cells . ^^^
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The validation of this strategy was supported by the demonstration that CART mRNA was profoundly reduced in obese rats with impaired leptin action , whether because of ablation of the ventromedial hypothalamus ( VMH ) or a loss of function mutation in the leptin receptor , as in Zucker diabetic fatty rats . ^^^
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Although the kidney expresses abundant transcripts of the short form of the leptin receptor ( Ob Ra ) , a role for this hormone in renal function remains unclear . ^^^ Furthermore , leptin receptor expression and potential signal transduction pathways were evaluated in GERs . ^^^
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Specificity of transcriptional changes in response to BDV infection is also suggested by the up regulation of cytokine and neuropeptide Y mRNAs associated with down regulation of pro opiomelanocortin , and with no change of IL 1R AcPI , dynorphin and leptin receptor mRNAs in the same brain region samples . ^^^
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The fact that estrone oleate had no effect on the leptin levels or expression in obese rats , in contrast with the marked inhibition observed in the lean suggests that the functionality of the leptin receptor is essential for estrone oleate inhibition of the ob gene . ^^^
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MEASUREMENTS : Several phenotypic measures of body fatness and fat distribution ( anthropometry ) , fasting plasma insulin , glucose and leptin concentrations , blood pressure and 2 h plasma glucose concentration , genotypes of subjects for the Gln223Arg , PRO1019pro ( OB R gene ) and OB gene polymorphisms . ^^^
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Reverse transcription polymerase chain reaction demonstrated that theca interstitial cells ( TIC ) from hypophysectomized rats expressed only a nonsignal transducing isoform ( OB Ra ) of leptin receptor mRNA . ^^^ In contrast , mRNAs for OB Ra and the signal transducing ( OB Rb ) leptin receptor isoforms were expressed in GC . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The present experiments sought to determine whether leptin regulates UCP 1 expression in BAT and its own expression in white adipose tissue ( WAT ) through the long or short forms of leptin receptor and modulation of norepinephrine release . ^^^ Lastly , db / db mice lacking the long form of the leptin receptor failed to increase UCP 1 mRNA in response to exogenous leptin but increased UCP 1 mRNA in response to CL 316 , 243 . ^^^ These studies establish that norepinephrine is required for leptin to regulate its own expression in WAT and UCP 1 expression in BAT and indicate that these effects are likely mediated through the centrally expressed long form of the leptin receptor . . ^^^
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The orexin A and B contents in the brains of obese Zucker rats that have disrupted leptin receptor were significantly higher than in their lean littermates , but in Otsuka Long Evans Tokushima Fatty rats that have disrupted cholecystokinin type A receptor the contents were similar to those of the controls . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of the long form of the leptin receptor , the isoform that is considered to have full signaling capability , has been reported in the central nervous system and several peripheral cell types . ^^^ In this study , the presence of leptin receptor variants and leptin action was evaluated in this cell line . ^^^ Messenger RNAs for both the long and a short form of the leptin receptor were detected by reverse transcription polymerase chain reaction ( RT PCR ) in AR42J cells , and authenticity of the receptor was confirmed by DNA sequencing . ^^^ These data demonstrate that the rat pancreatic tumor cell line AR42J expresses a functional form of the leptin receptor that modulates the action of CCK in calcium mobilization and amylase release . . ^^^
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In humans , mutations in leptin , leptin receptor , prohormone convertase 1 ( PC 1 ) , pro opiomelanocortin ( POMC ) , melanocortin 4 receptor ( MC 4 R ) , and peroxisome proliferator activated receptor ( PPAR ) gamma 2 genes have been described in patients with severe obesity . ^^^ These mutations suggest the critical role of central signaling systems composed of leptin / leptin receptor and alpha melanocyte stimulating hormone / MC4 R in human energy homeostasis . ^^^
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We here show that in CHO cells stably expressing the long form of the leptin receptor ( CHO OBRl ) , leptin induces transient expression of endogenous SOCS 3 mRNA but not of CIS , SOCS 1 , or SOCS 2 mRNA . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
With the use of RNase protection assays , we measured mRNA levels of interleukin 1beta ( IL 1beta ) , IL 1 receptor antagonist ( IL 1RA ) , IL 1 receptor type 1 ( IL 1RI ) , IL 1R accessory proteins ( AcP 1 and 2 ) , tumor necrosis factor alpha ( TNF alpha ) , transforming growth factor beta 1 ( TGF beta 1 ) , glycoprotein 130 ( Gp 130 ) , leptin receptor ( OB R ) , neuropeptide Y ( NPY ) , preprodynorphin , and proopiomelanocortin ( POMC ) . ^^^
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Mutation in the leptin receptor ( Leprfa ) causes fat storage independent hyperleptinaemia in neonatal rats . ^^^
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Recently , we have shown that in rodent Leydig cells leptin inhibits hCG stimulated testosterone ( T ) production via a functional leptin receptor isoform ; others have found that leptin inhibits basal and hCG induced T secretion by testis from adult rats . ^^^
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Pre and postprandial expression of the leptin receptor splice variants OB Ra and OB Rb in murine peripheral tissues . ^^^ Leptin receptors ( OB R ) are widely distributed in peripheral tissues . ^^^
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Mutations in the gonadotropin releasing hormone receptor , leptin , and the leptin receptor cause autosomal recessive HH . ^^^
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Leptin receptor in human term placenta : in situ hybridization and immunohistochemical localization . ^^^ On human term placenta tissue slices , digoxigenin UTP labelled RNA probe detected the long form of the leptin receptor ObR ( L ) mRNA in syncytiotrophoblasts of the villi , whereas the haematological subtype of the leptin receptor ObR / B219 . 1 was detected in blood cells of the intervillous space and fetal vessels . ^^^ Immunohistochemistry , with two polyclonal antibodies to the N terminus recognizing ObR ( L ) and ObR ( S ) of the leptin receptors and one to the C terminus recognizing the long form of the leptin receptor ObR ( L ) , localized leptin receptor protein at the apical membrane of the syncytiotrophoblasts . ^^^ Our results show that the long form of the leptin receptor ObR ( L ) is expressed in human term placentae . ^^^ We localized the long form of leptin receptor mRNA to the cytoplasm of syncytiotrophoblasts and leptin receptor proteins in human term placentae to the apical membrane of syncytiotrophoblasts . ^^^
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Inhibitory effects of leptin related synthetic peptide 116 130 on food intake and body weight gain in female C57BL / 6J ob / ob mice may not be mediated by peptide activation of the long isoform of the leptin receptor . ^^^ In this study , we used two in vitro bioassays to show that the interaction of LEP ( 116 130 ) with the long form of the leptin receptor ( OB Rb ) , the receptor isoform that is predominantly expressed in the hypothalamus , is not required for the observed in vivo effects of the peptide on energy balance . ^^^ LEP ( 116 130 ) was unable to compete the binding of alkaline phosphatase leptin fusion protein to OB R . ^^^
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RT PCR studies showed that rat Leydig cells express both the long ( OB Rb ) and short isoform ( OB Ra ) of leptin receptor , whereas MLTC 1 cells ( a murine Leydig tumor cell line ) express only the long isoform . ^^^ To probe this hypothesis , we first analyzed the expression of leptin receptors ( OB R ) in rodent Leydig cells in culture . ^^^
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Development changes in long form leptin receptor expression and localization in rat brain . ^^^ The expression and localization of long form leptin receptor ( OB Rb ) were studied immunocytochemically in the brain of fetal and adult rats using a polyclonal antibody that specifically recognized OB Rb . ^^^
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Leptin and leptin receptor expression in a lipoblastoma in an 8 year old girl . ^^^ RNA was isolated from a lipoblastoma of an 8 year old girl and the expression of leptin and leptin receptor mRNA was analyzed by RT PCR . ^^^ Whether or not leptin and leptin receptor expression play a role in the development and / or progression of lipoblastoma and other tumors is not clear to date . ^^^
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Reverse transcriptase polymerase chain reaction ( RT PCR ) for leptin receptor isoforms was performed on gastric epithelial cells isolated by laser capture microdissection . ^^^ In contrast , expression of both Ob R ( L ) and the leptin receptor isoforms could be detected in gastric epithelial cells . ^^^ Leptin receptor protein was detected throughout the mucosa . ^^^
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Glucoresponsive neurons displayed leptin receptor immunoreactivity , which was widespread in both enteric plexuses . ^^^
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Analysis of Tyr to Phe and fa / fa leptin receptor mutations in the PC 12 cell line . ^^^ Herein , we analyse the effect of mutations in the mouse leptin receptor using the PC 12 pheochromocytoma cell line as a model system . ^^^ Tyr to Phe mutations in the cytoplasmic tail of the mouse leptin receptor confirmed the critical role of Tyr 1138 ( a YxxQ motif ) and STAT 3 activation for induction of leptin induced genes in PC 12 . ^^^ The short isoform of the leptin receptor showed complete loss of stimulation of both genes . ^^^ In contrast , a leptin receptor devoid of all Tyr residues in its cytoplasmic tail was still capable of a limited induction of the PAP 1 gene . ^^^
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Detection and regulation of leptin receptor mRNA in ovine mammary epithelial cells during pregnancy and lactation . ^^^ Furthermore , quantitative determinations , via ribonuclease protection assays , provided evidence that the level of leptin receptor expression was greatest during mid pregnancy when active growth of the mammary gland is initiated . ^^^ Location of the leptin receptors , as determined by in situ hybridization analysis , revealed that leptin receptor transcripts were expressed specifically in mammary epithelial cells . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Two genetic models , the ob / ob mouse ( deletion of leptin protein ) and the db / db mouse ( deletion of leptin receptor ) have markedly augmented research in obesity . ^^^
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Leptin and leptin receptor expression in rat and mouse pituitary cells . ^^^ Leptin receptor messenger RNA was also examined in these tissues by RT PCR . ^^^ The long isoform of leptin receptor ( OB Rb ) was present in normal pituitary and in various pituitary cell lines , including FS , GH 3 , and alphaT 3 1 cells . ^^^ The finding of leptin and of the long isoform of leptin receptor in normal rat and mouse pituitaries and in various cell lines implicates an autocrine / paracrine loop in the production and regulation of leptin and leptin receptor in the rodent pituitary . . ^^^
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Systemic administration of leptin at doses ranging from 0 . 1 to 10 mg / kg / day induced a highly significant acceleration in wound repair in ob / ob mice ( p < 0 . 0001 ) , but not in db / db mice , indicating that leptin ' s effects on wound repair were mediated through the leptin receptor . ^^^ In addition , we found that all forms of leptin receptor , including the signal transducing long form , were present in skin by RNase protection assay , and that leptin receptor localized to subcutaneous vessels of wounded skin by in situ hybridization . ^^^
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Long and short forms of leptin receptor are expressed in differentiated C2C12 myotubes . ^^^
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However , leptin receptor is expressed not only in the central nervous system , but also in other systems such as reproductive and hematopoietic tissues . ^^^ These results demonstrate the presence of the leptin receptor in human circulating CD 4 ( + ) and CD 8 ( + ) T lymphocytes and a functional role of leptin as a modulator ( enhancer ) of lymphocyte stimulation with a shift toward Th 1 cytokine production profile . ^^^
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Associations between the leptin receptor gene and adiposity in middle aged Caucasian males from the HERITAGE family study . ^^^ Linkage and association studies between three exonic polymorphisms in the leptin receptor gene and body composition variables in the HERITAGE Family Study were undertaken . ^^^ These results indicate a significant effect of leptin receptor on adiposity in middle aged Caucasian males . . ^^^
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Photoperiod regulates arcuate nucleus POMC , AGRP , and leptin receptor mRNA in Siberian hamster hypothalamus . ^^^ Both adipose tissue leptin and ARC leptin receptor ( OB Rb ) mRNAs were downregulated in SDs , whereas FD increased OB Rb gene expression . ^^^
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Other studies have identified mutations within the genes that code for leptin ( LEP ) and its receptor ( LEPR ) , which have been linked to obesity in mice and humans . ^^^ Microsatellites proximal to leptin and leptin receptor as risk factors for spina bifida . ^^^
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Sequence analysis of cDNA fragments showed a deletion of one G residue located in exon 12 of the leptin receptor gene . ^^^
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LY 294002 prevented phosphatidylinositol bisphosphate , but not PtdIns ( 3 , 4 , 5 ) P ( 3 ) , from increasing K ( ATP ) channel activity , consistent with the latter lipid acting as a membrane associated messenger linking leptin receptor activation and K ( ATP ) channels . ^^^ Although PtdIns ( 3 , 4 , 5 ) P ( 3 ) appears a plausible and attractive candidate for the messenger that couples K ( ATP ) channels to leptin receptor activation , direct measurement of PtdIns ( 3 , 4 , 5 ) P ( 3 ) demonstrated that insulin , but not leptin , increased global cellular levels of PtdIns ( 3 , 4 , 5 ) P ( 3 ) . ^^^
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In order to examine the involvement of leptin in the ossification of spinal ligaments ( OSL ) , the present study examined ( 1 ) serum levels of leptin and insulin in OSL patients and controls , ( 2 ) serum leptin levels in children of OSL females with severe obesity , ( 3 ) the expression of leptin receptor mRNA in human spinal ligaments , and ( 4 ) effects of leptin on cultured human ligament cells . ^^^ The expression of leptin receptor mRNA was confirmed in the ligaments , but leptin did not influence the alkaline phosphatase activity nor procollagen type 1 carboxyl terminal peptide content of the ligament cells . ^^^
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Gestational profile of leptin messenger ribonucleic acid ( mRNA ) content in the placenta and adipose tissue in the rat , and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation . ^^^ In order to study this issue further , levels of the mRNA encoding the different leptin receptor isoforms were determined in the hypothalamus of pregnant and nonpregnant rats . ^^^ We found a specific reduction of the mRNA levels encoding the leptin receptor isoform Ob Rb in the hypothalamus of pregnant rats compared to nonpregnant animals , suggesting that during pregnancy the hypothalamus shows a physiological resistance to the high levels of leptin due , at least in part , to a decrease in the expression of the long , biologically active form of the leptin receptor ( Ob Rb ) . ^^^ In the hypothalami of these animals , Ob Rb mRNA content was similar to that observed in nonpregnant rats , but we found an increased expression of some of the short forms of the leptin receptor ( Ob Re and Ob Rf ) . ^^^
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Well differentiated hepatoma cells ( Fao ) possess both the long and short forms of the leptin receptor and respond to leptin with a stimulation of c fos gene expression . ^^^
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It has also recently been shown that leptin plays a promoting role in angiogenesis , and the vascular endothelium expresses the long form of leptin receptor . ^^^
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In our investigations in sheep , we have cloned a partial cDNA corresponding to the ovine long form leptin receptor , presumably the only fully active form , and have localized the long form leptin receptor in the ventromedial and arcuate nuclei of the hypothalamus . ^^^ Leptin receptor mRNA expression was colocalized with NPY mRNA containing cell bodies in those regions . ^^^ We have also determined that hypothalamic leptin receptor expression is greater in feed restricted ewes than in well fed ewes . ^^^
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Leptin deficiency and defects in the leptin receptor both produce human obesity . ^^^
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Decreased transport of leptin across the blood brain barrier in rats lacking the short form of the leptin receptor . ^^^ The short form of the leptin receptor has been hypothesized to be the transporter , with impaired transport of leptin being implicated in obesity . ^^^ In Koletsky rats , the splice variant that gives rise to the short form of the leptin receptor contains a point mutation that results in marked obesity . ^^^ The results indicate that the short form of the leptin receptor is involved in the transport of leptin across the BBB . . ^^^
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Similar effects were observed in lean and obese male Zucker rats , suggesting that the effect of EGCG was independent of an intact leptin receptor . ^^^
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Characterization and functional role of leptin receptor in bovine adrenal medullary cells . ^^^ We report here the characterization and functional roles of the leptin receptor ( ObR ) in bovine adrenal medullary cells . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin is an adipocyte derived hormone , that belongs structurally to the long chain helical cytokine family such as interleukin 2 ( IL 2 ) , interleukin 12 ( IL 12 ) , growth hormone ( GH ) , and signals by a class 1 cytokine receptor ( Ob R ) . ^^^
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Insulin resistance , role of leptin and leptin receptor ] . ^^^
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Molecular genetic analysis revealed a partial deletion of the leptin receptor ( Lepr , Ob R ) gene including the coding sequences downstream of exon 17 ' . ^^^ Partial leptin receptor gene deletion in transgenic mice prevents expression of the membrane bound isoforms except for Ob Rc . ^^^
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Here we describe the long term examination of a transgenic mouse line showing the disruption of the leptin receptor ( Lepr , Ob R ) gene caused by transgene insertion . ^^^ Contrasting obesity phenotypes uncovered by partial leptin receptor gene deletion in transgenic mice . ^^^ The leptin receptor defective mice of this line might serve as a model for the investigation of genes modulating the development and mode of expression of diabetes . . ^^^
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Likewise , there were no stressor effects on transforming growth factor beta 1 , neuropeptide Y , glycoprotein 130 , or leptin receptor mRNAs in brain regions . ^^^
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In adult animals , signaling through the leptin receptor ( OB R ) has been shown to play a critical role in fat metabolism . ^^^
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Leptin , the product of the ob gene , is a hormone mainly secreted by the adipose tissue , which acts through specific receptors ( Ob R ) widely distributed in the body tissues . ^^^
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Leptin receptor transcripts are constitutively expressed in placenta and adipose tissue with advancing baboon pregnancy . ^^^ To further characterize this model with regard to leptin function , messenger RNA transcripts for both long ( Ob RL ) and short ( Ob RS ) leptin receptor isoforms were identified in maternal tissues at various stages of gestation . ^^^ The expression of leptin receptor transcripts in maternal adipose tissues , as well as in the syncytiotrophoblast , amniochorion , decidua , and corpus luteum , suggests the potential for autocrine / paracrine roles for the polypeptide in the endocrinology of primate pregnancy . ^^^
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Autosomal recessive HH may be brought about by mutations in the gonadotropin releasing hormone receptor , leptin , and the leptin receptor genes . ^^^
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The long form of the leptin receptor ( OB Rb ) is widely expressed in the human brain . ^^^
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Expression of leptin receptor ( Ob R ) in human atherosclerotic lesions : potential role in intimal neovascularization . ^^^ Leptin , via activation of the endothelial receptor ( Ob R ) , generates a growth signal involving a tyrosine kinase dependent intracellular pathway and promotes angiogenic processes . ^^^
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Determination of leptin receptor in the serum and relations to laboratory and anthropological parameters in patients with atherosclerotic complications . ^^^ Then we analyzed concentration of leptin receptor ( double sandwich ELISA , standard recombinant human leptin ) , leptin , glucose , insulin , proinsulin , CRP and uric acid in the serum . ^^^ The control group was subjected to determination of BMI , leptin and leptin receptor in the serum . ^^^ Concentration of leptin receptor does not differ significantly between the patients with atherosclerosis and normal population . ^^^ Probands with atherosclerosis showed a very close negative correlation between concentration of leptin receptor and leptinemia which is absent in normal population . . ^^^
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Regulation of leptin receptor , POMC and AGRP gene expression by photoperiod and food deprivation in the hypothalamic arcuate nucleus of the male Siberian hamster ( Phodopus sungorus ) . ^^^
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Low dose leptin caused a significant increase in 17 , 20 lyase activity in adrenal NCI H295R cells expressing leptin ( OB ) receptor ( OB R ) , without significant sustained influence on the 17alpha hydroxylase activity . ^^^
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Localization of leptin receptor like immunoreactivity in the corticotropes , somatotropes , and gonadotropes in the ovine anterior pituitary . ^^^ The presence of the leptin receptor ( LR ) has been demonstrated in the endocrine and neuroendocrine tissue , but only limited information is available regarding cell specific expression in the anterior pituitary gland . ^^^
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There is little or no expression of the long form leptin receptor in primary rat hepatocytes , and these signaling events are probably mediated through the short forms of the leptin receptor . ^^^
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One of its targets in the central nervous system appears to be the epithelial cells of the choroid plexus where leptin receptor ( OB R ) expression is particularly high . ^^^ In addition , our experiments suggest that leptin is rapidly internalized upon binding to these cells supporting the view of an OB R mediated transport of leptin across the choroid plexus . . ^^^
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When Chinese hamster ovary cells expressing the rat leptin receptor were stimulated with recombinant canine leptin produced by E . coli , some intracellular signal transduction proteins were phosphorylated , indicating that the recombinant leptin was biologically active . ^^^
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Structure and tissue distribution of chicken leptin receptor ( cOb R ) mRNA . ^^^ Chicken leptin receptor ( cOb R ) cDNA has been cloned , sequenced and characterized . ^^^ The predicted cOb R preprotein was composed of 1148 amino acids showing approximately 60 % sequence identity with the long isoform of mammalian leptin receptor , and contained a putative signal peptide , a single transmembrane domain and the conserved box 1 , 2 and 3 motifs in the cytoplasmic region . ^^^
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Disorders of leptin receptor structure and function one of the causes of obesity ? ] . ^^^
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Effect of cerebroventricular infusion of insulin and ( or ) glucose on hypothalamic expression of leptin receptor and pituitary secretion of LH in diet restricted ewes . ^^^ The objective was to determine the effect of central infusion of insulin and ( or ) glucose on hypothalamic expression of leptin receptor and pituitary secretion of LH in the ewe . ^^^ Leptin receptor mRNA expression was dramatically reduced ( P < 0 . 0002 ) in INS+GLU versus aCSF treated ewes . ^^^
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Polymerase chain reaction restriction fragment length polymorphism ( PCR RFLP ) assay for the mouse leptin receptor ( Lepr ( db ) ) mutation . ^^^ A PCR RFLP assay for genotyping at the mouse leptin receptor ( Lepr ( db ) ) mutation site was developed using modified primers . ^^^
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Leptin receptor and leukemia . ^^^ Leukemic cells of some patients with acute myeloblastic leukemia , acute lymphoblastic leukemia , and chronic myeloid leukemia ( CML ) also express the leptin receptor . ^^^ In cases of CML , higher expression of leptin receptor is observed during blast crisis than in chronic phase . ^^^
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Using hypothalamic explants from Zucker rats homozygous for the leptin receptor mutation ( fa / fa ) , GnRH pulse frequency was not affected by leptin , while a significant acceleration was caused by the CART peptide . ^^^
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Using PC 12 cells as an in vitro model system , we have identified a series of transcripts induced through activation of the leptin receptor . ^^^
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Activation of downstream signals by the long form of the leptin receptor . ^^^ The adipocyte derived hormone leptin signals the status of body energy stores by activating the long form of the leptin receptor ( LRb ) . ^^^
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Association of Trp64Arg polymorphism of the beta 3 adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity . ^^^ OBJECTIVE : To investigate whether Trp64Arg polymorphism of the beta 3 adrenergic receptor ( beta 3 AR ) gene and Gln223Arg polymorphism of the leptin receptor ( Ob R ) gene are associated with obesity in Japanese schoolchildren . ^^^
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The ' fatty ' ( Glu269Pro ) leptin receptor mutation causes severe obesity associated with hypertriglyceridaemia and altered hepatic apolipoprotein gene regulation in Zucker fatty rats . ^^^ CONCLUSIONS : Interactions of the ' fatty ' leptin receptor mutation with the genetic background significantly affect the basal and diet induced regulation of the apoA 4 , C 3 and A 1 genes in rat liver . ^^^
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Leptin receptor mediated regulation of cholinergic neurotransmitter phenotype in cells of central nervous system origin . ^^^ The leptin receptor ( OBR ) shares sequence similarity and signaling capabilities with receptors for cytokines of the ciliary neurotrophic factor ( CNTF ) family . ^^^ In this cell line , termed SN 56 / OBR , leptin induces STAT transcription factor activation and STAT dependent reporter gene expression in a manner similar to that of CNTF . ^^^ Furthermore , in SN 56 / OBR cells both CNTF and leptin produce changes in neurotransmitter and neuropeptide phenotype characteristic of cholinergic neurons , such as an increase in choline acetyltransferase and vasoactive intestinal polypeptide , and a decrease in neuropeptide Y expression . ^^^ SN 56 / OBR cells thus constitute an interesting new model system to investigate leptin action in cells of central nervous system origin . ^^^
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The long isoform of leptin receptor is widely distributed in brain , whereas numerous short forms are also being present in peripheral tissues . ^^^
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Leptin itself stimulates CNS leptin receptors ( OB r receptor ) which link with pro opiomelanocortin ( POMC ) / MC 4 receptors . ^^^
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This radiolabeled analog has been used to characterize and localize central and peripheral leptin binding sites ( Ob R ) of the mouse at different stages of its development . ^^^
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Transcellular transport of leptin by the short leptin receptor isoform ObRa in Madin Darby Canine Kidney cells . ^^^ We previously reported that rat brain microvessels , which constitute the blood brain barrier , contain large amounts of messenger RNA encoding a short form of the leptin receptor ( ObRa ) , suggesting that this site may be important for receptor mediated transport of leptin into the brain . ^^^
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The biological activity of bovine leptin , porcine leptin , and porcine leptin analogue W4R / R5K was evidenced by their ability to stimulate proliferation of leptin sensitive BAF / 3 cells transfected with a long form of human leptin receptor . ^^^
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The faK mutation is a premature stop codon in the extracellular domain of the leptin receptor , resulting in a natural receptor knockout . ^^^
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Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle . ^^^ Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors ( OB R ) . ^^^ Accumulated evidence shows that leptin is involved in the stimulation of reproductive functions and that local expression of leptin and OB R in the ovary , oocyte , embryo , and placenta plays a role in early development . ^^^ To investigate the role of leptin in implantation , we examined the expression of OB R and leptin in the human endometrium . ^^^ The present results indicate that OB R , but not leptin , is expressed in the human endometrium . . ^^^
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Effects of leptin and cholecystokinin in rats with a null mutation of the leptin receptor Lepr ( fak ) . ^^^ The Koletsky ( `` corpulent ) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor ( Lepr ) that results in hyperphagia , obesity , and hyperlipidemia . ^^^ Because the Lepr ( fak ) mutation is null , exogenous leptin should have no effect on body weight or food intake in fa ( k ) / fa ( k ) rats . ^^^
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B219 / OB R 5 ' UTR and leptin receptor gene related protein gene expression in mouse brain and placenta : tissue specific leptin receptor promoter activity . ^^^ Leptin receptor ( OB R ) splice variants either encode proteins with different 3 ' cytoplasmic domains or have different 5 ' untranslated regions ( UTR ) , indicative of dual promoters . ^^^ The B219 / OB R promoter transcribes only OB R transcripts , whereas the OB R / GRP promoter initiates transcription of both OB R and another protein of unknown function , called the leptin receptor gene related protein ( OB RGRP ) . ^^^ We thus assessed , by inference , the contributions of the two promoters to the leptin receptor transcript pool , in murine brain or in placenta , a tissue with abundant leptin receptor mRNA . ^^^ OB RGRP mRNA ( and thus by inference OB R / GRP promoter activity ) was widely distributed in murine brain , with elevated expression in the hypothalamic regions that express the leptin receptor mRNA , including the paraventricular nucleus . ^^^
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Expression of the long form of leptin receptor ( Ob Rb ) mRNA in the brain of mouse embryos and newborn mice . ^^^ The long form of the leptin receptor ( Ob Rb ) has a cytoplasmic domain which activates the JAK STAT signal transduction pathway . ^^^
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The mammalian leptin receptor ( LEPR ) ( formerly OB R ) mediates the weight regulatory effects of the circulating hormone leptin . ^^^ The extreme obese phenotype of recessive mutations in the mouse leptin or LEPR genes ( ob / ob and db / db mice , respectively ) indicate the high potential of these genes for medical and agricultural research . ^^^ In this paper , we report on the cloning of the full length chicken leptin receptor ( CLEPR ) cDNA , which is the first non mammalian cloning of a LEPR gene . ^^^ Molecular cloning and properties of the chicken leptin receptor ( CLEPR ) gene . ^^^
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AIMS / HYPOTHESIS : The Zucker fatty fa / fa rat develops hyperinsulinaemia , insulin resistance and severe obesity as a result of a homozygous mutation in the leptin receptor gene . ^^^
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Transcriptional and posttranscriptional regulation of the leptin receptor , NPY , and POMC genes . ^^^ This article focuses on the regulation of the leptin receptor , NPY , and POMC genes , and explores what is known about the regulation of these obesity genes in response to food intake or changes in body fat stores . ^^^
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Ultrastructural localization of the leptin receptor in the rat hypothalamus was studied by immunocytochemistry . ^^^ The antiserum against the leptin receptor which was used specifically recognized the carboxy terminal of the cytoplasmic domain . ^^^ Intense leptin receptor immunoreactivity was detected in the arcuate , paraventricular , and ventromedial nuclei of the hypothalamus and in the lateral hypothalamic area . ^^^ At the ultrastructural level , leptin receptor like immunoreactivity appeared to be concentrated predominantly in perikarya and dendrites of these areas and strong immunolabeling for the leptin receptor was detected in the plasma membrane , rough endoplasmic reticulum , Golgi apparatus , and cytoplasmic matrix . ^^^ This study provides the first detailed fine structure of leptin receptor immunoreactive neurons in the rat hypothalamus . ^^^
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Obese Zucker rats ( fa / fa ) are characterized by inadequate leptin signaling caused by a mutation in the leptin receptor gene . ^^^
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We also investigated the coexpression of Fos IR and the long form of the leptin receptor ( OBRb ) mRNA . ^^^
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By comparison , the effects of diabetes to increase hypothalamic neuropeptide Y ( NPY ) expression and to decrease corticotropin releasing hormone ( CRH ) expression were normalized by insulin treatment , whereas the expression of mRNA encoding the long form of the leptin receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment . ^^^
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Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture . ^^^ In addition to fat cells , endothelial cells were immunopositive for the full length leptin receptor . ^^^ The cellular and subcellular localization of leptin and its receptor ( Ob receptor [ Ob R ] ) and their relationship to various stages of fat cell maturation have not been characterized as yet . ^^^ Therefore , we analyzed leptin and Ob R by using reverse transcriptase polymerase chain reaction , immunohistochemistry , and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation . ^^^ The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob R . ^^^
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The leptin receptor protein was shown to be expressed in glandular and luminal epithelium and is periodically regulated throughout the menstrual cycle , demonstrating main expression in follicular and mid luteal phase . ^^^ In contrast , leptin receptor mRNA is detectable by reverse transcription polymerase chain reaction ( RT PCR ) as a constitutive component . ^^^ These patients were , however , deficient for expression of the functional leptin receptor . ^^^ These analyses provide evidence that the lack of the leptin receptor in an ovulatory cycle may contribute to subfertility by a yet undefined ' endometrial factor ' . . ^^^
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The expression of leptin receptor isoforms Ob Ra and Ob Rb mRNA was detected by RT PCR analysis of total RNA from primary cultured glial cells . ^^^ Protein of leptin receptor was also expressed in mouse primary cultured glial cells as evaluated by Western blotting analysis . ^^^
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Leptin and leptin receptor mRNA were first detected in the brain and hypothalamus but now their ubiquitous presence has been demonstrated . ^^^ Leptin receptor signal transduction involves the activation of signal transducer and activator of transcription ( STAT ) 3 , a member of the transcription family of proteins . ^^^
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Thus , leptin rapidly activates signaling pathways directly at the level of insulin sensitive tissues through the long form leptin receptor , and these pathways overlap with , but are distinct from , those engaged by insulin . . ^^^
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Expression of Agrp is markedly increased in the hypothalamus of mice deficient in leptin ( Lep ( ob ) / Lep ( ob ) ) or its receptor ( Lepr ( db ) / Lepr ( db ) ) , suggesting that leptin mediates signals suppressing Agouti related protein production . ^^^ Effects of leptin receptor mutation on Agrp gene expression in fed and fasted lean and obese ( LA / N faf ) rats . ^^^ We , therefore , analyzed the expression of Agrp in the medial basal hypothalamus of lean ( + / + , + / fa ( f ) ) and obese leptin receptor deficient ( fa ( f ) / fa ( f ) ) LA / N rats . ^^^
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Recently , leptin and leptin receptor expression were demonstrated in non tumorous and adenomatous human pituitaries . ^^^
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Leptin receptor was immunolocalized to the syncytiotrophoblast . ^^^ No change was observed in the expression of the leptin receptor in either the growth retarded or diabetic pregnancies . ^^^
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These findings strongly suggest that the leptin receptor ( OB R ) in the BBB can be easily saturated . ^^^ Saturation of the BBB OB R in obese individuals would explain the defect in leptin transport into the brain described in this study . . ^^^
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Expression of the leptin receptor during germ cell development in the mouse testis . ^^^ We investigated the expression of the leptin receptor ( Ob R ) in testes from different age groups . ^^^
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Because GALP mRNA in the Arc appeared to overlap with the known distribution of leptin receptor mRNA , we tested the hypothesis that GALP expression is regulated by leptin . ^^^
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The expression of long form leptin receptor mRNA was detected in fetal adipose tissue . ^^^
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The leptin receptor , including the signalling splice variant , was also identified in specific fetal tissues . ^^^ The physiological importance of expression of both leptin and the leptin receptor ( OB R and OB Rb ) in the placenta remains to be determined . ^^^
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However , monogenic obesity has been described in a few families due to changes in leptin , leptin receptor , prohormone convertase , pro opiomelanocortin or melanocortin 4 receptor . ^^^
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Furthermore , polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion ; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity , with elevated and low blood pressure , respectively . ^^^
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The biological activity of the C4S analog was evidenced by its ability to stimulate proliferation of leptin sensitive BAF / 3 cells transfected with a long form of human leptin receptor construct similar to its nonmutated counterpart , indicating that Cys 4 plays no role in leptin activity . ^^^
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We now know that leptin signals through its receptor , OB R , which is a member of the cytokine receptor superfamily . ^^^
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Porcine leptin receptor : molecular structure and expression in the ovary . ^^^ The porcine leptin receptor complementary DNA was cloned and sequenced and the leptin receptor gene expression evaluated in the porcine ovary . ^^^ Leptin receptor mRNA was present in porcine kidney , liver , spleen , lung , brain , testis , uterus , ovary , corpus luteum ( CL ) , theca , and granulosa cells . ^^^ The abundance of leptin receptor transcripts and protein varied during luteinization of granulosa cells in vitro and in the CL during the pig luteal phase . ^^^ Leptin receptor mRNA was present in granulosa cells at isolation and increased in abundance as the cells luteinized over 96 hr in culture . ^^^
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Persistence of blood to brain transport of leptin in obese leptin deficient and leptin receptor deficient mice . ^^^ Radioiodinated leptin was intravenously injected into ob / ob ( no leptin production ) and db / db ( high leptin levels , but no long form leptin receptor ) mutant mice and their lean controls . ^^^
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Soluble leptin receptor in serum of subjects with complete resistance to leptin : relation to fat mass . ^^^ Leptin resistance and obesity have been related to mutations of the leptin receptor gene in rodents and , recently , in a consanguineous family . ^^^ Western blot analysis showed a band at 146 kDa reacting specifically with an antibody directed against the leptin receptor ectodomain . ^^^ In 10 obese control subjects , as in the mutated patients , free leptin levels correlated with BMI ( r = 0 . 70 , P = 0 . 0011 ) and reflected fat mass , regardless of leptin receptor functioning . ^^^ This finding suggests that the leptin receptor itself may not be specifically involved in the control of leptin secretion , and it supports the concept of relative resistance to leptin in common obesity . . ^^^
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Leptin and leptin receptor immunoreactivity was detected in C 6 cells , suggesting a possible autocrine role for leptin . ^^^ Using RT PCR analysis a product of the expected size for the short , but not the long , leptin receptor isoform was detected in C 6 cells . ^^^
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Homology modeling of human leptin / leptin receptor complex . ^^^ Leptin receptor mediates the weight regulatory signal carried by the adipocyte secreted peptide hormone , leptin . ^^^ However , the structure of leptin receptor has not yet been determined . ^^^ Leptin shows structural similarity to G CSF , while leptin receptor is similar in amino acid sequence to G CSF receptor . ^^^ Because of the similarity between leptin / leptin receptor complex and G CSF / G CSF receptor complex , we tried to build a model structure of leptin / leptin receptor complex with the crystal structure of the G CSF / G CSF receptor complex as the template . ^^^
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The common pentanucleotide polymorphism of the 3 ' untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non diabetic men : a prospective case control study . ^^^ OBJECTIVES : The purpose of the study was to test whether the pentanucleotide insertion / deletion polymorphism in the 3 ' untranslated region ( 3 ' UTR ) of the leptin receptor gene , which has previously been associated with serum insulin levels in obese subjects , is associated with insulin levels and the risk of type 2 diabetes in non diabetic middle aged men . ^^^
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Leptin ( ob gene ) and its cognate receptor ( obr ) are relevant for fat metabolism . ^^^
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The long isoform of leptin receptor belongs to the cytokine receptors group . ^^^
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Long form leptin receptor mRNA expression in the brain , pituitary , and other tissues in the pig . ^^^ This study was conducted to determine the location of long form leptin receptor ( Ob Rl ) mRNA in various tissues of the pig . ^^^ The leptin receptor has several splice variants in the human and mouse , but Ob Rl is the major form capable of signal transduction . ^^^
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The adipocyte hormone , leptin , has homology with tumor necrosis factor alpha ( TNF alpha ) and the leptin receptor ( OB Rb ) has homology with the interleukin ( IL ) 6 receptor . ^^^
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Leptin produced a 5 fold induction of luciferase activity in CV 1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA . ^^^
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Leptin receptor , NPY , POMC mRNA expression in the diet induced obese mouse brain . ^^^ The aim of this study is to characterize the mRNA levels of leptin receptor ( LR ) , neuropeptide Y ( NPY ) and pro opiomelanocortin ( POMC ) in high fat ( HFF ) and low fat ( LFF ) fed groups of mice . ^^^ The hypothalamic arcuate nucleus ( Arc ) was investigated , as was the choroid plexus ( ChP ) in the case of the leptin receptor . ^^^ The present results suggest that in the middle stage of development of high fat induced obesity , when central leptin sensitivity is maintained , the increased leptin receptor expression may play a role to defend against obesity which is overwhelmed as central leptin insensitivity develops . ^^^
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Long form leptin receptor ( OB R ( L ) ) is a signal transducing member of the cytokine receptor superfamily that is essential for mediating the effects of leptin on mammalian body weight homeostasis . ^^^ At present , the range of transcriptional targets responsive to OB R ( L ) activation , and consequently , the likely mediators of leptin action , remain undefined . ^^^ In this report , we have used cDNA subtractive hybridization to identify transcripts induced by leptin in immortalized hypothalamic neurons expressing OB R ( L ) . ^^^
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In the past decade , there have been major advances in our understanding of the molecular genetics and pathogenesis of obesity , especially with regards to the genetics and functions of chemical mediators and their receptors , such as leptin , the leptin receptor , neuropeptide Y , the melanocortin 4 receptor , agouti related protein and the peroxisome proliferator activated receptor gamma 2 . ^^^
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Expression of leptin and leptin receptor isoforms in the human stomach . ^^^ Information on leptin and leptin receptor expression in the human stomach is lacking . ^^^ METHODS : Fundic and antral gastric mucosal biopsies , primary cultures of human gastric epithelial cells , and the human gastric cancer cell line AGS were screened for expression of leptin and different leptin receptor isoform mRNA by reverse transcriptase polymerase chain reaction . ^^^ Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa . ^^^
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The obese diabetic db / db mouse , which has defects in leptin receptor , displays enhanced neural responses and elevated behavioral preference to sweet stimuli . ^^^ Taste tissue ( circumvallate papilla ) of lean mice expressed leptin receptor mRNA and some of the taste cells exhibited immunoreactivities to antibodies of the leptin receptor . ^^^
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In animal obesity , defective hypothalamic leptin receptor activation prevent leptin from acting , with resulting obesity , insulin and leptin resistance . . ^^^
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The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance . ^^^
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Leptin deficiency or leptin receptor defects produce massive obesity . ^^^
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Therefore , 51 yr old men ( N = 284 ) were selected ; and anthropometric , endocrine , metabolic , and hemodynamic variables were examined in relation to polymorphisms of the leptin receptor gene ( LEPR ) , by restriction fragment length polymorphism technique . ^^^ When BMI and leptin are elevated , increased blood pressure is found only with the most prevalent LEPR genotype at codons 109 and 223 , whereas variants of this receptor seem to protect from hypertension . ^^^ Hypertension in obesity and the leptin receptor gene locus . ^^^ Recent animal studies indicate that leptin is involved in the regulation of blood pressure through the leptin receptor . ^^^ These results suggest that leptin is associated with blood pressure regulation in men through the leptin receptor . ^^^
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Leptin was measured in serum and vitreous by radioimmunoassay , and leptin and leptin receptor were localized in epiretinal membranes immunohistochemically . ^^^ Leptin and leptin receptor were detected in fibrovascular epiretinal membrane of patients with diabetes . ^^^
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Polycystic ovarian syndrome ( PCOS ) is often associated with obesity and insulin resistance , both of which are features that are linked to the leptin and leptin receptor ( LEPR ) genes . ^^^ In conclusion , PCOS is not commonly a consequence of mutations of the leptin or LEPR genes . ^^^ No evidence for mutations of the leptin or leptin receptor genes in women with polycystic ovary syndrome . ^^^
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Differential expression of leptin receptor in high and low fat fed Osborne Mendel and S5B / Pl rats . ^^^ Ribonuclease protection assays and Western blotting were used to assay the levels of mRNA and protein , respectively , for short ( ObR S ) and long ( ObR L ) forms of the leptin receptor in the hypothalamus . ^^^ This investigation determined if altered expression of leptin receptors ( ObR ) in the hypothalamus could potentially contribute to altered sensitivity to diet induced obesity between OM and S5B / P1 rats . ^^^
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Single gene defects leading to obesity have been discovered in animals and , in some cases , confirmed in humans as congenital leptin deficiency or congenital leptin receptor deficiency . ^^^
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CNTF exerts its actions through activation of a receptor complex , which shows similarity of sequence , second messenger systems and distribution to the leptin receptor . ^^^
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Possible adverse interactions between an usually inconspicuous genetic trait and early environmental factors favoring the development of obesity were investigated in rats heterozygous for the leptin receptor defect `` fatty ' ' ( fa ) . ^^^
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SOCS 3 mediates feedback inhibition of the leptin receptor via Tyr 985 . ^^^ During leptin signaling , each of the phosphorylated tyrosine residues on the long form of the leptin receptor ( LRb ) mediates distinct signals . ^^^
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Although the short form of the leptin receptor is involved in leptin transport , it appears that other mechanisms of entry also exist . ^^^
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A missense mutation of the leptin receptor induces hyperphagia and obesity in the obese Zucker fa / fa rat . ^^^
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Our demonstration that the signalling or long form ( Ob Rb ) of the leptin receptor is present in both primary adult osteoblasts and chondrocytes suggests that the growth promoting effects of leptin could be direct . ^^^
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In the hypothalamus , topiramate increased mRNA for neuropeptide Y , reduced mRNA for neuropeptide Y Y 1 and Y 5 receptors , corticotropin releasing hormone ( CRH ) , and type 2 glucocorticoid receptors but had no effect on mRNA levels for the short or long form of the leptin receptor . ^^^
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Differential regulation of leptin receptor but not orexin in the hypothalamus of the lactating rat . ^^^ In addition , in the presence of chronically suppressed levels of serum leptin , there may be a change in leptin receptor expression in the hypothalamus . ^^^ The objectives of the present study were to determine if orexin and leptin receptor mRNA levels were changed during lactation . ^^^ There was a significant increase in leptin receptor mRNA levels in the supraoptic nucleus during lactation compared to dioestrus . ^^^ Furthermore , leptin receptor protein , as determined by immunocytochemistry , was colocalized in virtually all vasopressin and oxytocin cells in the supraoptic nucleus . ^^^
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Diacylglycerol kinase zeta in hypothalamus interacts with long form leptin receptor . ^^^
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We show that a catalytically inactive mutant of SHP 2 blocks leptin stimulated ERK phosphorylation by the long leptin receptor , ObRb . ^^^ Analysis of signaling by ObRb lacking intracellular tyrosine residues or by the short leptin receptor , ObRa , enabled us to conclude that two pathways are critical for ERK activation . ^^^
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Mapping of the leptin receptor gene ( LEPR ) to chicken chromosome 8 . ^^^
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Direct double labeling immunofluorescence histochemistry of sections from control mice , combining a goat antiserum raised against a peptide sequence present in all leptin receptor isoforms ( Ob R ) or a guinea pig anti serum generated to a peptide sequence specific for Ob Rb with rabbit STAT 3 antiserum , demonstrated colocalization of STAT 3 and Ob R as well as colocalization of STAT 3 and Ob Rb , in many cell bodies of the arcuate nucleus . ^^^ The results suggest that circulating leptin acts via leptin receptor / STAT3 containing neurons in the ventral arcuate nucleus and that congenital leptin deficiency , as seen in obese ob / ob mice , results in a down regulation of STAT 3 mRNA and protein levels . . ^^^
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We have now examined the mRNA levels of PPAR alpha , delta , and gamma in three murine models of obesity , namely , ob / ob ( leptin deficient ) , db / db ( leptin receptor deficient ) , and serotonin 5 HT2c receptor ( 5 HT2cR ) mutant mice . 5 HT2cR mutant mice develop a late onset obesity that is associated with higher plasma leptin levels . ^^^
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Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation . ^^^ We hypothesize that leptin resistance is associated with hypothalamic leptin receptor downregulation . ^^^ In addition , we show a downregulation of leptin receptor mRNA and protein in the hypothalamus , which may be one of the mechanisms by which the food intake effects of leptin were lost . . ^^^
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METHODS : Leptin receptor mRNA and c fos mRNA were measured by RT PCR . ^^^ In fetal pancreatic islets , both the common extracellular portion ( OB R ) and the intact long form ( OB Rb ) of the leptin receptor were readily detected by reverse transcriptase polymerase chain reaction . ^^^
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Fluorescence in situ hybridization of scarce leptin receptor mRNA using the enzyme labeled fluorescent substrate method and tyramide signal amplification . ^^^ To increase the sensitivity of fluorescence in situ hybridization ( FISH ) for detection of low abundance mRNAs , we performed FISH on cryostat sections of rat hypothalamus with biotin labeled riboprobes to leptin receptor ( ObRb ) and amplified the signal by combining tyramide signal amplification ( TSA ) and Enzyme Labeled Fluorescent alkaline phosphatase substrate ( ELF ) methods . ^^^ Then biotin labeled leptin receptor hybrids were detected with the TSA ELF method . ^^^ Combining the ELF and TSA amplification techniques enabled FISH detection of scarce leptin receptor mRNAs and permitted the identification of leptin receptor mRNA in cells that also express NPY and POMC gene products . . ^^^
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Genetically obese rodents with mutations of leptin or the leptin receptor are defective in leptin signaling and develop morbid obesity and diabetes . ^^^ The latter conclusion was supported by three lines of evidence : 1 ) The soluble leptin receptor is up regulated by about 20 fold in Zucker Diabetic Fatty rats ; 2 ) Adenovirus mediated overexpression of the soluble leptin receptor results in a similar fold increase of circulating leptin ; 3 ) In ob / ob mice , which have no endogenous leptin , exogenously administered leptin reaches a higher level when the soluble leptin receptor is overexpressed . ^^^ The weight reducing effect of leptin is enhanced in C57Bl / 6 ob / ob mice with overexpression of the soluble leptin receptor . ^^^ Soluble leptin receptor may be a significant factor determining the amount of total leptin in circulation . . ^^^
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Gene expression in the hypothalamic arcuate nucleus for leptin receptor ( OB Rb ) , POMC , and melanocortin 3 receptor ( MC 3 R ) was higher in LD but did not change from weaning levels in SD . ^^^
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Identification of the Y 985 and Y 1077 motifs as SOCS 3 recruitment sites in the murine leptin receptor . ^^^ Herein we describe how suppressor of cytokine signalling 3 ( SOCS 3 ) , a potential mediator of this leptin resistance is recruited into the activated murine leptin receptor complex . ^^^ Using a functional assay based on inhibition of leptin mediated reporter induction , and using phosphopeptide affinity chromatography we show binding of SOCS 3 to the highly conserved phosphorylated Tyr 985 and Tyr 1077 motifs within the mouse leptin receptor . . ^^^
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Impaired neural regulation of insulin secretion related to the leptin receptor gene mutation in Wistar fatty rats . ^^^ A homo allelic leptin receptor gene mutation has been reported in ZF rats . ^^^
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Homologous and heterologous down regulation of leptin receptor messenger ribonucleic acid in rat adrenal gland . ^^^ Secondly , semi quantitative RT PCR analysis indicated a complex pattern of adrenal leptin receptor ( Ob R ) mRNA expression , with predominant expression of the Ob Ra and Ob Rb isoforms , as well as moderate levels of the Ob Rc and Ob Rf variants , whereas negligible signals for the Ob Re isoform were detected . ^^^ Interestingly , such an expression pattern appeared hormonally regulated as exposure to human recombinant leptin ( 10 ( 7 ) M ) or ACTH ( 10 ( 7 ) M ) significantly decreased Ob R isoform mRNA expression . ^^^ Overall , our results provide evidence for a novel regulatory step at the level of Ob R mRNA expression in the interplay between ACTH and leptin for the tuning of rat adrenal corticosterone secretion . ^^^ Furthermore , our data showing down regulation of Ob R mRNA expression by its cognate ligand may well be relevant to leptin physiology and its alteration in various disease states . . ^^^
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Expression and intracellular localization of leptin receptor long isoform GFP chimera . ^^^ The leptin receptor ( OBR ) and its ligand leptin ( OB ) are key players in the regulation of body weight . ^^^ Taken together , our results provide novel data concerning the intracellular trafficking of the two different isoforms of the leptin receptor . . ^^^ In both SHSY5Y and HEK 293 cells transfected with OBR ( l ) GFP , a predominant intracellular green OBR ( l ) GFP fluorescence was detected in vesicles also positive for internalized fluorophore conjugated leptin . ^^^ In biotinylation streptavidin pulse chase experiments , using antibodies raised against GFP and OBR , we observed that the rate of early appearance of OBR ( s ) at the cell surface , upon leptin stimulation , was faster than that found for OBR ( l ) GFP . ^^^
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OBJECTIVES : The role of the leptin receptor ( LEPR ) gene Gln223Arg polymorphism on the metabolic and body composition changes in response to overfeeding was studied . ^^^ Leptin receptor Gln223Arg variant is associated with a cluster of metabolic abnormalities in response to long term overfeeding . ^^^
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In the second stage of analysis , an important chromosome 1 positional candidate gene , the leptin receptor ( LEPR ) , was studied . ^^^ RESULTS : Multipoint analysis of the genome scan data identified linkage ( log of odds , LOD , 3 . 4 ) of leptin levels to a chromosomal region defined by D1S3728 and D1S1665 , flanking the leptin receptor ( LEPR ) gene by approximately 9 and 3 cM , respectively . ^^^ Two polymorphic DNA markers in LEPR and their haplotypes revealed linkage to unadjusted and adjusted BMI and leptin , and an association with leptin levels was found as well . ^^^ CONCLUSION : These data provide evidence that a human chromosome 1 locus , harboring the LEPR gene , contributes to plasma leptin concentrations , adiposity and body weight in humans affected with this insulin resistant dyslipidemic syndrome . ^^^
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Leptin receptor expression and suppressor of cytokine signaling transcript levels in high fat fed rats . ^^^ In this experiment we assessed whether feeding of a high fat diet to rats affects leptin receptor ( OB R ) transcript levels or induces up regulation of the suppressors of leptin / cytokine induced signaling , SOCS 3 and PIAS 3 . ^^^ We found that despite a significant weight gain associated with markedly increased circulating leptin levels neither OB R gene expression nor SOCS 3 or PIAS 3 mRNA levels were significantly altered in the high fat fed rats . ^^^
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Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst . ^^^ In the present study , we describe for the first time the expression of leptin and leptin receptor ( long form ) in the secretory endometrium and that endometrial leptin secretion is regulated in vitro by the human blastocyst . ^^^ Leptin and leptin receptor messenger RNA and protein were identified in secretory endometrium and in cultured endometrial epithelial cells ( EECs ) by RT PCR , Western blot , and immunohistochemistry . ^^^
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Localization of long form leptin receptor in the somatostatin containing neurons in the sheep hypothalamus . ^^^ To ascertain the extent to which leptin may act on these neurons , we have used immunohistochemistry to examine co localization of long form of the leptin receptor ( OB Rb ) and SRIF in the sheep hypothalamus . ^^^
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It is well known that mouse placenta produces the secretory isoform of the leptin receptor , OB Re . ^^^ Leptin levels , as determined by the RIA , might therefore provide artificially high values when serum levels of the secretory form of OB R are high , in cases , for example , such as the last period of pregnancy in mice . . ^^^
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In a group of randomly selected 29 healthy prepubertal children ( 16 boys , mean age 9 . 56 + / 0 . 7 years , 13 girls , mean age 9 . 96 + / 0 . 9 years ) fasting serum leptin and leptin receptor concentrations were measured by ELISA and compared with insulin parameters ( homeostatic model of assessment insulin resistance = HOMA IR , insulin , intact proinsulin , C peptide ) and some metabolic parameters and factors that contribute to insulin resistance : triacylglycerols , high density lipoprotein cholesterol ( HDL cholesterol ) , low density lipoprotein cholesterol , body mass index , tumor necrosis factor , heart fatty acid binding protein , and IgG fraction of anticardiolipin . ^^^ Serum leptin concentrations were tightly correlated with body mass indexes and negatively correlated with leptin receptor concentrations , probably as a manifestation of down regulation . ^^^
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Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells : implications for leptin ' s actions . ^^^ Four splice variants of the leptin receptor have been identified in humans : the long isoform that has full intracellular signaling capacity and 3 shorter isoforms that differ in the length of their cytoplasmic tail . ^^^ Here , we report the quantification by reverse transcriptase polymerase chain reaction ( RT PCR ) of the relative expression levels of the 2 major leptin receptor splice variants , the long ( OB RL ) and the shortest membrane bound variant ( OB RS ) in mononuclear cells from peripheral blood of 15 healthy human subjects ( 9 women and 6 men ) , with a body mass index ( BMI ) that ranged from 19 . 7 to 41 . 6 . ^^^ In conclusion , the expression of OB RS and OB RL leptin receptor isoforms appears to be reduced in human peripheral blood mononuclear cells from obese individuals , with OB RS remaining the predominant leptin receptor isoform . ^^^
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These direct leptin effects are supported by the presence of the long form of the leptin receptor , considered to be capable of performing intracellular signaling , in peripheral tissues , including skeletal muscle . ^^^ The understanding of the putative direct leptin signaling pathway in skeletal muscle could be an important step towards the utilization of leptin or a leptin receptor agonist as therapeutic tools to treat obesity and its related metabolic disorders . . ^^^
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In the present study we investigated the acute modulatory effects of food intake stimulated leptin secretion on HPA axis activity and hypothalamic leptin receptor ( Ob Rb ) expression in 24 hour fasting , adult female , BALB / c mice after insulin induced hypoglycemia . ^^^
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The Zucker diabetic fatty ( ZDF ) rat is a model of type 2 diabetes and , like the human disease , has both insulin resistance ( from a mutant leptin receptor causing obesity ) and inadequate beta cell compensation . ^^^ This study demonstrates that the ZDF rat carries a genetic defect in beta cell transcription that is inherited independently from the leptin receptor mutation and insulin resistance . ^^^
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Three rare cases of human morbid obesity of early onset associated with hypogodatropic hypogodanism are due to mutations in the leptin and the leptin receptor genes . ^^^
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Quantitative trait loci for obesity and insulin resistance ( Nob 1 , Nob 2 ) and their interaction with the leptin receptor allele ( LeprA720T / T1044I ) in New Zealand obese mice . ^^^ The leptin receptor variant of NZO ( LeprA720T / T1044I ) failed to alter any of the variables of obesity . ^^^
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Serum leptin and leptin receptor isoforms in omental adipose tissue of nondiabetic women undergoing gynecologic surgery for benign disease . ^^^ The leptin receptor isoforms in tissues were quantified using real time Taqman technology . ^^^ RESULTS : Three leptin receptor isoforms , Ob Rb , HuB219 . 1 , and HuB219 . 3 , were found in human omental adipose tissue . ^^^ Higher body mass index was significantly correlated with an increase in serum leptin concentration and a decrease in leptin receptor HuB219 . 1 isoform in omental fat , even after adjustment for age and menopausal status . ^^^ CONCLUSIONS : HuB219 . 1 is the major isoform of leptin receptor expressed in human omental adipose tissue . ^^^
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This effect of leptin on monocytic cells requires the presence of the functional leptin receptor OB Rb , which we have shown to be present in human monocytes by RT PCR and by measuring the activation of the Jak / STAT pathway . ^^^
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Developmental and hormonal regulation of leptin receptor ( Ob R ) messenger ribonucleic acid expression in rat testis . ^^^ In target tissues , leptin receptor ( Ob R ) gene expression results in an array of alternatively spliced isoforms ( Ob Ra to Ob Rf ) with different functional features . ^^^
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Mechanisms for LEPR mediated regulation of leptin expression in brown and white adipocytes in rat pups . ^^^ To investigate the underlying mechanisms for leptin receptor ( LEPR ) mediated regulation of leptin gene ( Lep ) expression in brown ( BAT ) and white ( WAT ) adipose tissue and resultant effects on plasma leptin concentrations ( plasma LEP ) , we examined effects of sympathetic nervous system ( SNS ) activity , caloric balance , and body fat content on leptin mRNA levels in BAT and WAT in 10 day old rat pups segregating for Lepr ( fa ) . ^^^
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This study examined differences in metabolism and ventilatory responsiveness in the Zucker ( Z ) and Koletsky ( K ) rat which each carry a different recessive mutation of the leptin receptor gene . ^^^
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Leptin receptor 5 ' untranslated regions in the rat : relative abundance , genomic organization and relation to putative response elements . ^^^ Mice heterozygous for a mutation in the leptin receptor ( leptin R ) have an increased body fat mass suggesting that the abundance of leptin R may be an important determinator of leptin sensitivity . ^^^
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In chorionic villous tissue , trophoblasts stained strongly positive for leptin receptor like immunoreactivity . ^^^ Two membrane bound isoforms of the leptin receptor were also detected in placental tissue . ^^^ In both umbilical and maternal serum , a soluble leptin receptor was found migrating as broad band at Mr 97 , 000 D . ^^^
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Several of leptin receptor isoforms were identified , including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform . ^^^ The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women . ^^^ Relationships of soluble leptin receptor levels to body mass index ( BMI ) , body fat content , serum leptin , TNF alpha and insulin levels were also studied . ^^^ The blood for the determination of leptin , soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting . ^^^ Serum soluble leptin receptor levels in patients with anorexia nervosa were significantly higher compared the to control group ( 24 . 67 + / 8 . 3 U . ml 1 vs . 15 . 71 + / 2 . 79 U . ml 1 , p < 0 . 01 ) . ^^^
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The leptin receptor ( OBR ) is a member of the class 1 cytokine receptor family and several different isoforms , produced by alternative mRNA splicing are found in many tissues , including the hypothalamus . ^^^
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One site of leptin ' s action is the central nervous system , where the leptin receptor ( Ob R ) messenger ribonucleic acid ( mRNA ) and protein are expressed in discrete areas . ^^^
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We examined the genetic contribution of single nucleotide polymorphisms ( SNPs ) of the energy metabolism related genes , including beta 3 adrenergic receptor ( beta3AR ) , apolipoprotein E ( apo E ) , promoter of uncoupling protein 3 ( UCP 3 p ) , peroxisome proliferator activated receptor gamma 2 ( PPARgamma 2 ) and leptin receptor ( LEPR ) to metabolic disorders , in 118 inhabitants of Palau . ^^^
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Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor . ^^^ Immunoreactivity for the leptin receptor was detected in normal , high grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium . ^^^
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The effect of treatment with a 0 . 03 % fatty acid ( FA ) cocktail on leptin receptor mediated STAT ( signal transducers and activators of transcription ) activation in the rat insulinoma cell line BRIN BD 11 was investigated . ^^^ TaqMan analysis of gene expression following chronic FA treatment showed neither a decrease in the amount of leptin receptor ( Ob R ) mRNA , nor an increase in the negative regulators of STAT signalling , SOCS 3 ( suppressors of cytokine signalling ) or cytokine inducible sequence ( CIS ) . ^^^
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Transcriptional responses to leptin are increased when transmitted through ObR mutated at Tyr 986 , the SHP 2 docking domain , yet this mutation does not alter the synergy between TGF beta and leptin . ^^^ Leptin signals through the Ob receptor , which is closely related to the gp 130 cytokine receptor . ^^^
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Conversely , db / db mice , which are deficient in the leptin receptor , had lower ghrelin mRNA levels than control mice . ^^^
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To investigate the possible role of galanin in mediating the physiological effects of leptin in the mouse , we had three experimental objectives : first , to map the distribution of galanin messenger RNA expressing cells in the brain of the mouse ; second , to assess the effects of leptin on galanin gene expression in areas of the brain thought to be involved in the regulation of body weight and reproduction ; and third , to determine whether galanin neurons in these regions express leptin receptor messenger RNA . ^^^ Galanin producing neurons in the arcuate , dorsomedial and periventricular nuclei did not appear to express leptin receptor messenger RNA ( P > 0 . 05 ) . ^^^
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Lean ( Fa / ? ; normal leptin receptor ; n = 7 ) and obese ( fa / fa ; mutated leptin receptor ; n = 8 ) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C ( 12 : 12 h light dark cycle ) for continuous ( 24 h ) measurement of metabolic and cardiovascular variables . ^^^
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More than 85 % of the GALP neurons were immunostained with leptin receptor antibody . ^^^
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Previous studies have generated conflicting data and , as there is little leptin receptor expressed in the lateral hypothalamus , it is likely that any observed leptin effects on these peptides are indirect . ^^^
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METHODS : The obese , diabetic db / db mouse , which lacks the functional full length Ob Rb leptin receptor , is a suitable model to assess the effects of hyperleptinemia on peripheral tissues that express other receptor isoforms . ^^^ RESULTS : A short form of the leptin receptor ( Ob Ra ) , but not Ob Rb , was present by reverse transcription polymerase chain reaction in the kidney and mesangial cells of both nondiabetic db / m and diabetic db / db mice . ^^^ We postulate that increased leptin levels may transmit a signal through the short form leptin receptor to up regulate TbetaRII and activate the intraglomerular TGF beta system , which may contribute to the glomerulosclerosis of obesity or type 2 diabetes . . ^^^
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We detected a leptin receptor on the PMN membrane by immunocytochemistry with an anti leptin receptor . ^^^ These results show for the first time that a functional leptin receptor is present on PMNs and that leptin may be able to influence their oxidative capacity . . ^^^
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However , only a subset of hypothalamic neurons expressing the long form of the leptin receptor ( Ob Rb ) also coexpress the neuronal activation marker Fos after leptin stimulation . ^^^
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These effects are mediated by the long isoform of the leptin receptor , because its transcript is expressed in the adrenal tissue . ^^^
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Phosphorylation of 985 and 1138 tyrosine of long form leptin receptor activates SHP 2 and STAT 3 , respectively . ^^^ Soluble leptin receptor concentrations in serum are negatively correlated with BMI . ^^^
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In this paper , we summarized the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities involved in the regulatory mechanism of appetite such as leptin , leptin receptor , POMC , MC 4 R and prohormone convertase 1 . . ^^^
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In this review , we describe leptin , leptin receptor , and potential hypothesis of leptin resistance . . ^^^
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Human obesity and point mutations of leptin and leptin receptor ] . ^^^ There have been reported point mutations of the genes correspond to leptin ( ob gene ) and leptin receptor ( db gene ) . ^^^
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Mice homozygous for the Leprdb3J ( db3J ) mutation are null for all known isoforms of the leptin receptor ( LEPR ) . ^^^ Transgenic complementation of leptin receptor deficiency . 1 . ^^^
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Genetic studies in obese mice have revealed the Ob . gene , its products leptin and the leptin receptor to be important factors in the regulation of both appetite and energy expenditure . ^^^ Leptin acts through the leptin receptor , which belongs to the cytokine receptor family . ^^^ In rodents as well as in humans , homozygous mutations in genes encoding leptin or the leptin receptor cause early onset morbid obesity , hyperphagia , and reduced energy expenditure . ^^^
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Human SNX 1 , 2 , and 4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases , including receptors for epidermal growth factor , platelet derived growth factor , and insulin as well as the long form of the leptin receptor , a glycoprotein 130 associated receptor . ^^^
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MATERIALS AND METHODS : A novel technique of laser capture microdissection was used to separate cortical and chromaffin cells for mRNA expression studies of leptin receptor isoforms and leptin mRNA in adrenal tissue and cell line NCI H 295 . ^^^ Immunostaining was used to localize leptin receptor in human adrenal slices . ^^^
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The virus was injected into the arcuate nucleus of mice that express Cre only in those neurons that express neuropeptide Y or the leptin receptor . ^^^
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These include mutations that cause leptin deficiency or leptin receptor inhibition and mutations that induce insulin , insulin like growth factors , or insulin responsive transcription factors . ^^^
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RT PCR analyses showed that both FS cell populations expressed the mRNAs for glial fibrillary acidic protein , S 100 protein , transforming growth factor beta 1 ( TGFbeta 1 ) , TGFbeta receptor , interleukin 6 , leptin , leptin receptor , pituitary adenylate cyclase activating polypeptide ( PACAP ) , and PACAP receptors . ^^^
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However , the effects of insulin and glucocorticoids on the components of the leptin system free leptin ( FL ) , bound leptin ( BL ) and soluble leptin receptor ( SR ) have not been elucidated . ^^^ MATERIAL AND METHODS : In the first of two studies ( study 1 ) , we measured free leptin ( FL ) , bound leptin ( BL ) , a soluble leptin receptor ( SR ) and insulin , by specific RIA methods , in six healthy subjects on a control day , and subsequently during a hyperinsulinaemic euglycaemic clamp study . ^^^ CONCLUSION : We conclude that insulin and dexamethasone increase free leptin levels , but do not change the concentrations of bound leptin and soluble leptin receptor . ^^^
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METHODS : We compared the fever responses to intravenous E . coli lipopolysaccharide ( 10 microg / kg ) between Zucker fa / fa ( obese due to a defective leptin receptor ) and Fa / . ( lean ) rats and between Otsuka Long Evans Tokushima Fatty ( OLETF ; obese due to the lacking cholecystokinin A receptor ) and Long Evans Tokushima Otsuka ( lean ) rats . ^^^
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Leptin receptor , beta 2 adrenergic receptor and glucocorticoid receptor gene polymorphisms have been associated with an augmented clustering of metabolic abnormalities in response to overfeeding . ^^^
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We found that J774 . 2 macrophages express the functional long form of the leptin receptor ( ObRb ) and that this becomes tyrosine phosphorylated after stimulation with low doses of leptin . ^^^
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Leptin receptor immunoreactivity is present in ascending serotonergic and catecholaminergic neurons of the rat . ^^^ Using double labelling immunohistochemistry we have studied the localisation of leptin receptor proteins including both long and short forms and their possible presence in serotonergic ( 5 HT ) and catecholaminergic neurons in the rat brain . ^^^ Leptin receptor immunoreactivity was found to be widely distributed in the central nervous system including cortical areas , amygdala , several hypothalamic and thalamic nuclei , the raphe system , pontine nuclei , locus coeruleus , parabrachial nucleus , tractus solitarus and the medullary reticular formation . ^^^ High degrees of co existence of leptin receptor immunoreactivity with serotonin in the raphe system were observed in B 1 , B 5 , B 6 , B 7 , B 8 and B 9 . ^^^ In B 3 and B 2 less than 50 % of the 5 HT cells colocalised leptin receptor immunoreactivity . ^^^
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A model of activation of the protein tyrosine phosphatase SHP 2 by the human leptin receptor . ^^^ Signalling through the leptin receptor has been shown to activate the SH 2 domain containing tyrosine phosphatase SHP 2 through tyrosine phosphorylation . ^^^ The human leptin receptor contains five tyrosine residues in the cytoplasmic domain that may become phosphorylated . ^^^ We show here using BIAcore studies , wherein binding of peptides to SHP 2 was detected , that peptides corresponding to sequences containing phosphotyrosines 974 and 986 ( LR974P and LR986P , respectively ) from the leptin receptor cytoplasmic domain were the only two peptides that bound to the enzyme . ^^^ Only the leptin receptor derived peptide corresponding to tyrosine 974 was dephosphorylated by recombinant purified SHP 2 . ^^^
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Cloning and characterization of a novel human leptin receptor overlapping transcript like 1 gene ( LEPROTL 1 ) . ^^^ The cDNA consists of 2701 bp and has a putative open reading frame encoding 131 amino acids which possesses a JAK binding site ( Pro ( 46 ) Ile Pro ( 48 ) which is preceded by a cluster of hydrophobic residues ) and is highly homologous to the leptin receptor gene related protein ( OB RGRP ) . ^^^
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Apolipoprotein D interacts with the long form leptin receptor : a hypothalamic function in the control of energy homeostasis . ^^^
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Furthermore , the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction , immunocytochemistry , and Western blot analysis . ^^^ We also identified the presence of leptin receptor in the mouse artery wall , localized to subpopulations of medial and adventitial cells , and the expression of leptin by artery wall cells and atherosclerotic lesions in mice . ^^^
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Soluble leptin receptor represents the main leptin binding activity in human blood . ^^^ Subjecting this preparation to size exclusion chromatography ( SEC ) we observed a coelution of leptin binding activity with levels of the soluble leptin receptor ( sOB R ) determined by a newly developed ligand immunofunctional assay . ^^^
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Structures and functions of leptin and leptin receptor ] . ^^^
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There was no effect on expression of the signal transducing form of the leptin receptor . ^^^
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A single nucleotide polymorphism ( SNP ) in the leptin receptor is associated with BMI , fat mass and leptin levels in postmenopausal Caucasian women . ^^^ These observations indicate that functional variations in the leptin receptor gene are important factors in the regulation of adiposity and BMI . . ^^^
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Immunohistochemistry confirmed that the epithelium and blood vessels located in the granulation tissue expressed the functional leptin receptor obRb isoform during skin repair . ^^^
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The aim of this study was to evaluate whether polymorphisms in the leptin receptor ( LEPR ) gene were related to obesity and body fat distribution phenotypes , such as waist and hip circumferences and the amount of visceral and subcutaneous fat . ^^^ Polymorphisms in the leptin receptor gene , body composition and fat distribution in overweight and obese women . ^^^ OBJECTIVE : Leptin is an adipocyte secreted hormone involved in body weight regulation , acting through the leptin receptor , localised centrally in the hypothalamus as well as peripherally , amongst others on adipose tissue . ^^^ CONCLUSION : In conclusion , polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women . ^^^ Since body fat distribution variables were adjusted for fat mass , these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity . . ^^^
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It is therefore possible that variation in the leptin receptor gene ( LEPR ) may contribute to obesity and influence birth weight . ^^^ Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations . ^^^ OBJECTIVE : This study investigates the influence of the leptin receptor gene variant Gln223Arg ( A > G , 668 ) , on maternal body mass index ( BMI ) , foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian ( India , Bangladesh , Pakistan ) and UK / Irish origin . ^^^ Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no significant association with foetal birth weight ( adjusted for gestational length ) or with maternal BMI during first trimester ( adjusted for age ) in either population group . ^^^ CONCLUSION : These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight , and is not associated with variation in maternal BMI in early pregnancy in our sample . . ^^^
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Developmental changes in the long form leptin receptor and related neuropeptide gene expression in the pig brain . ^^^ The long form leptin receptor ( Ob Rl ) is localized within the hypothalamus along with several neuropeptides that are involved in regulation of the neuroendocrine axis . ^^^
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Proopiomelanocortin ( POMC ) and neuropeptide Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators , melanocortins and neuropeptide Y , which exert opposing effects on feeding and metabolism . ^^^
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However , leptin receptor gene expression was detected in the ovine placenta , suggesting that the placenta is a target organ for leptin . ^^^ The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and / or fetal development . . ^^^
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BACKGROUND : In humans , a mutation of the leptin receptor gene ( LEPR ) leads to a rare obese syndrome of mendelian inheritance . ^^^ These results indicate that variations at the leptin receptor locus are associated with common obesity phenotypes and are a part of the polygenic influences on the response to nutritional environment . . ^^^
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Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium . ^^^ The mRNA and protein of the long form leptin receptor ( OB R ( L ) ) but not of leptin are expressed in the human endometrium and the abundance of OB R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase . ^^^
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Regulation of leptin and leptin receptor in baboon pregnancy : effects of advancing gestation and fetectomy . ^^^ Leptin ( LEP ) and leptin receptor ( LEP R ( L ) and LEP R ( S ) isoforms ) messenger ribonucleic acids ( mRNAs ) were quantitated by competitive RT PCR , and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues . ^^^
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Obese , diabetic C57BL / Ks db / db mice that lack the long form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin . ^^^
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To examine the potential role of hypothalamic pathways in the hyperphagia and obesity of OLETF rats , we compared patterns of hypothalamic neuropeptide Y ( NPY ) , proopiomelanocortin ( POMC ) , and leptin receptor mRNA expression in ad libitum fed Long Evans Tokushima ( LETO ) and OLETF rats and food restricted OLETF rats that were pair fed to the intake of LETO controls . ^^^
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GABA neurones in the ventromedial arcuate nucleus were shown to contain leptin receptor immunoreactivity , as revealed using an antiserum generated to a sequence common to all isoforms of the leptin receptor ( Ob R ) , as well as an antiserum generated to the carboxy terminal end of the long leptin receptor ( Ob Rb ) , and immunoreactivity for the leptin induced signal transduction molecule STAT 3 . ^^^ The presence of leptin receptor and STAT 3 in GABAergic arcuate neurones , but absence of changes in gene transcription for GAD and VGAT mRNA suggests , that leptin does not transcriptionally regulate the expression of proteins involved in GABAergic transmission in arcuate neurones . ^^^
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Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr ( db / + ) mice : effects on placental leptin and fetal growth . ^^^
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Leptin secretion and leptin receptor in the human stomach . ^^^ Here we investigate the possible presence of leptin and leptin receptor in the human stomach . ^^^ METHODS : Leptin and leptin receptor expression were assessed by immunohistochemistry , reverse transcriptase polymerase chain reaction ( RT PCR ) , and western blot analysis on biopsy samples from 24 normal individuals . ^^^ The leptin receptor was present in the basolateral membranes of fundic and antral gastric cells . mRNA encoding Ob RL was detected in both the corpus and antrum , consistent with a protein of approximately 120 kDa detected by immunoblotting . ^^^ CONCLUSION : These data provide the first evidence of the presence of leptin and leptin receptor proteins in the human stomach and suggest that gastric epithelial cells may be direct targets for leptin . ^^^
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Leptin receptor long form signalling in a human liver cell line . ^^^ Expression of the long form of the leptin receptor was detected by reverse transcriptase polymerase chain reaction ( RT PCR ) and Western blotting in the human liver cell line WRL 68 . ^^^ WRL 68 cells therefore provide the first human in vitro hepatocyte system in which to study leptin receptor mediated signalling and to elucidate the role of leptin in liver . . ^^^
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Recently , the long and active isoform of the leptin receptor was detected in the ovary , indicating that leptin may also show direct gonad related activity . ^^^
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To determine if leptin signal transduction is impaired in response to central administration of leptin and whether reduced hypothalamic leptin receptors may be contributing to the impaired signal transduction , we examined the in vivo dose response leptin induced STAT 3 activation ( phosphorylation and binding activity to the SIE M 67 oligonucleotide ) in response to i . c . v . administration of leptin along with the level of hypothalamic leptin receptor protein in young and older , late onset obese rats . ^^^ Leptin increased phosphorylation of STAT 3 transcription factor binding eight fold in the young but only four fold in the aged obese rats , and leptin receptor protein was 50 % greater in the young compared with aged rats . ^^^ These data indicate that aged overweight rats demonstrate reduced signal transduction in response to centrally administered leptin that may be the result of the diminished leptin receptor protein observed in the aged obese rats . ^^^
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Recently , leptin has been found to generate a growth signal involving a tyrosine kinase dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor ( Ob R ) in endothelial cells . ^^^ We have examined the expression of matrix metalloproteinases ( MMPs ) and tissue inhibitors of metalloproteinases ( TIMPs ) and Ob R in human atherosclerotic lesions , leptin mediated angiogenesis in vivo and in vitro . ^^^ The immunohistological analysis of the leptin treated rat cornea showed definitive rises in Ob R , MMPs and TIMPs expression as well as those of VEGF receptor ( VEGFR 1 ) . ^^^
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We therefore investigated the relationship between circulating plasma concentrations of leptin and insulin and immunoreactivity in the endocrine pancreas for leptin and leptin receptor ( OB R ) in genetically normal rats that were programmed to become obese during adult life . ^^^
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Molecular mechanisms of leptin action in adult rat testis : potential targets for leptin induced inhibition of steroidogenesis and pattern of leptin receptor messenger ribonucleic acid expression . ^^^ The focus of this study was twofold : ( 1 ) to identify potential targets for leptin induced inhibition of steroidogenesis , and ( 2 ) to characterize in detail the pattern of expression and cellular distribution of leptin receptor ( Ob R ) mRNA in adult rat testis . ^^^ In addition , our data on the pattern of testicular expression of Ob R isoforms and cellular distribution of Ob R mRNA may help to further elucidate the molecular mechanisms of leptin action in rat testis . . ^^^
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However , individual MCH levels were not directly correlated to leptin levels in the lean ( functional leptin receptor ) or in the obese ( non functional leptin receptor ) Zucker rats . ^^^
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Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve . ^^^ By using reverse transcription polymerase chain reaction , mRNAs encoding long ( Ob Rb ) and short ( Ob Ra ) leptin receptor isoforms were detected in the rat nodose ganglion , which contains the cell bodies of the vagal afferent neurons . ^^^ Western blot analysis confirmed the presence of leptin receptor immunoreactive proteins in extracts from the vagal trunk . ^^^ In cervical vagal segments , levels of leptin receptor protein displayed physiological regulation , with decreased amounts after feeding and increased levels after food restriction . ^^^ In addition , leptin receptor and STAT 3 immunoreactivities were detected in neurons of the nucleus of tractus solitarius ( NTS ) and the dorsal motor nucleus of the vagus nerve ( DMNX ) by immunofluorescence histochemistry . ^^^
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The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin ( AM ) , its receptor ( AM R ) and leptin , which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor ( OB Rb ) . ^^^
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Leptin receptor ( OB R ) gene expression in human primary osteoblasts : confirmation . ^^^
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A role for dietary fat in leptin receptor , OB Rb , function . ^^^ Much is known about the structure of the functional , or long , form of the leptin receptor , OB Rb . ^^^
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Recent evidence has pointed toward a possible role of leptin ( Lep ) and its receptor ( Lepr ) in early gestation materno fetal cross talk . ^^^ However , in gestating sows , exhaustive characterization of leptin mRNA expression in backfat and leptin receptor mRNA expression in endometrial and embryonic tissues is still pending . ^^^
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Genes currently recognized to be involved comprise KAL ( associated with 10 linked KS ) , the GnRH receptor ( associated with resistance to GnRH therapy ) , DAX 1 ( associated with adrenohypoplasia congenita ) and three loci also associated with obesity , leptin ( OB ) , leptin receptor ( DB ) and prohormone convertase ( PC 1 ) . ^^^
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The leptin receptor exists in numerous isoforms , the long isoform being the major form involved in signal transduction . ^^^ The long isoform of the leptin receptor has also been shown to be present in pituitary adenomas ; however , contrasting results have been obtained regarding its expression in the normal human pituitary . ^^^ RESULTS : Leptin receptor long isoform expression was detected in 2 / 4 GH secreting adenomas , 12 / 17 non functioning adenomas , 5 / 9 ACTH secreting adenomas , 1 / 2 prolactinomas , 2 / 2 FSH secreting adenomas and 5 / 5 normal pituitaries . ^^^
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Homozygosity for a null allele of the carbonic anhydrase 2 gene ( Car2n ) does not alter IOP while homozygosity for a mutation in the leptin receptor gene ( Leprdb ) that causes obesity and diabetes results in increased IOP . ^^^
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The leptin receptor is a member of the class 1 cytokine receptor family , and its signal transduction resembles that induced by many cytokines . ^^^ We demonstrated that serially cultured human articular chondrocytes possess the leptin receptor ( Ob R ) , and that this receptor was present on chondrocytes in native human cartilage . ^^^ In cultured chondrocytes we detected mRNA for the functional isoform of leptin receptor ( Ob Rb or Ob R ( L ) ) , and it was revealed that ligand binding resulted in phosphorylation of signal transducers and activators of transcription , namely STAT 1 and STAT 5 . ^^^
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Expression of leptin ( Ob ) and leptin receptor ( Ob R ) in human fibroblasts : regulation of leptin secretion by insulin . ^^^
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The fact that genetic defects can result in human obesity has been unequivocally established over the past 3 years with the identification of the genetic defects responsible for different monogenic forms of human obesity : the leptin , leptin receptor , pro opiomelanocortin , pro hormone convertase 1 and melanocortin 4 receptor genes . ^^^
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This study describes the generation of such a system using chinese hamster ovary ( CHO ) cells that were transfected with the long form of the rat leptin receptor isoform , OB Rb , whereby a signal transduces and activators of transcription sensitive luciferase reporter system is further employed to quantify the leptin mediated signals . ^^^
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Short day weight loss was accompanied by reduced POMC and leptin receptor ( OB Rb ) mRNA in the arcuate nucleus but elevated cocaine and amphetamine regulated transcript . ^^^
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Generation of human soluble leptin receptor by proteolytic cleavage of membrane anchored receptors . ^^^ The leptin receptor ( ObR ) exists in multiple isoforms . ^^^ In conclusion , human leptin binding protein is generated by proteolytic cleavage of membrane anchored leptin receptor by a metalloprotease . . ^^^ Ligand mediated immunofunctional and immunofluorometric assays revealed that the leptin binding protein in medium bound both leptin and an ObR specific antibody and that the level of leptin binding protein correlated with receptor expression at the cell surface . ^^^
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The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability . ^^^ Genetic variation at the leptin receptor gene locus may play an important role in the pathophysiology of human obesity , a leptin resistant state . ^^^ Previous studies exploring potential associations between leptin receptor gene polymorphisms and obesity have reported conflicting results . ^^^ The aim of this study was to evaluate a genetically homogeneous population for associations between body composition variables and three common leptin receptor gene polymorphisms ( K109R , Q223R , and K656N ) that have potential functional significance as well as to assess the contributions of these polymorphisms to the variability of obesity . ^^^ These findings support the hypothesis that the Q223R polymorphism ( but not the K109R or K656N polymorphism ) of the leptin receptor gene is associated with obesity and predicts a small percentage of body weight and body composition variability in a genetically homogeneous population . . ^^^
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Hexosamines and nutrient excess induce leptin production and leptin receptor activation in pancreatic islets and clonal beta cells . ^^^ In the present study we found that glucosamine rapidly activates the production of leptin and OB Rb , which encodes the functional leptin receptor , in both primary pancreatic islets and clonal beta cells . ^^^
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These results suggest that dietary fat alters brain apo E levels , which may be regulated , in part , through the leptin receptor . . ^^^
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Expression and localization of leptin receptor in the normal rat pituitary gland . ^^^ Leptin receptor ( leptin R ) is a polypeptide consisting of a single transmembrane spanning component . ^^^
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Analysis by RT PCR also demonstrated a decreased expression of leptin receptor mRNA in old animals . ^^^
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Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno fetal leptin physiology during late pregnancy , and elicits hypertension associated with hyperleptinaemia in the early growth retarded adult offspring . ^^^ OBJECTIVE : To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations , the placental expression of leptin or the short form of the leptin receptor ( ObR S ) , or combinations thereof , and to evaluate whether hypertension or hyperinsulinaemia in the early growth retarded adult progeny of dexamethasone treated dams is associated with altered leptin concentrations . ^^^ Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy . ^^^
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However , the leptin receptor is expressed not only in the central nervous system , but also in other systems , such as reproductive , hematopoietic , and immune tissues , suggesting various roles in addition to the regulation of food intake and energy expenditure . ^^^ The leptin receptor bears homology to members of the class 1 cytokine receptor family . ^^^ We have recently found that the leptin receptor is expressed not only in monocytes but also in both CD 4 ( + ) and CD 8 ( + ) T lymphocytes . ^^^ In this paper , we have studied the signal transduction of the leptin receptor in peripheral blood mononuclear cells . ^^^ These results indicate that human leptin receptor in circulating mononuclear cells has the signaling capacity to activate JAK STAT cascade . ^^^
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Anti leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads . ^^^ An anti leptin receptor polyclonal antibody ( receptor antibody ) , as well as leptin , stimulated the release of free fatty acids from isolated mouse fat pads in a time dependent manner . ^^^ The receptor antibody did not show any additive effect to the stimulation of lipolysis induced by leptin , suggesting that they exert their actions through a similar mechanism involving the leptin receptor . ^^^
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RNA expression for the leptin receptor ( Ob R ) was detectable in human PBMCs . ^^^ The percentage of cells expressing leptin receptor was 25 + / 5 % for monocytes , 12 + / 4 % for neutrophils , and 5 + / 1 % for lymphocytes ( only B lymphocytes ) . ^^^
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Insulin inhibits leptin receptor signalling in HEK 293 cells at the level of janus kinase 2 : a potential mechanism for hyperinsulinaemia associated leptin resistance . ^^^
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Selective deletion of leptin receptor in neurons leads to obesity . ^^^ Animals with mutations in the leptin receptor ( ObR ) exhibit an obese phenotype that is indistinguishable from that of leptin deficient ob / ob mice . ^^^ ObR is expressed in many tissues , including brain , and the relative importance of leptin ' s effects on central versus peripheral sites has not been resolved . ^^^ The obese mice with low levels of hypothalamic ObR also show elevated plasma levels of leptin , glucose , insulin , and corticosterone . ^^^ To explore possible direct effects of leptin on a peripheral tissue , we also characterized ObR ( Alb ) KO mice . ^^^
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We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor ( Ob Rb ) expressed in cultured porcine chromaffin cells . ^^^
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RESULTS : Human preadipocytes and adipocytes from lean and obese subjects expressed the long leptin receptor isoform and two of the three short forms as assessed by polymerase chain reaction ( PCR ) . ^^^
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To examine these two potentially pathogenic forces , we studied Zucker rats ( leptin receptor wild type , + / + ; heterozygous , + / ; and mutant , / ) . ^^^
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Removal of adrenal steroids by adrenalectomy ( ADX ) slows or reverses the development of many forms of obesity in rodents , including those that are leptin or leptin receptor deficient . ^^^ We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase ( JAK ) signal transducers and activators of transcription ( STAT ) signaling pathway . ^^^ ADX increased the expression of leptin receptor mRNA , increased STAT 3 mRNA and protein levels , induced constitutive STAT 3 phosphorylation and DNA binding activity , and also reduced suppressor of cytokine signaling 3 ( SOCS 3 ) mRNA and protein levels . ^^^
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Myocytes were isolated from the db / db mouse , a leptin receptor mutant that develops symptoms of non insulin dependent ( type 2 ) diabetes . ^^^
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The thrombi that form when leptin receptor deficient obese ( db / db ) mice are injured also are unstable . ^^^ Platelets express the leptin receptor , and leptin potentiates the aggregation of platelets from ob / ob but not db / db mice in response to known agonists . ^^^
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Immunohistochemical characterization of localization of long form leptin receptor ( OB Rb ) in neurochemically defined cells in the ovine hypothalamus . ^^^ The long isoform ( OB Rb ) is the major signaling form of the leptin receptor in the hypothalamus . ^^^
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Additionally , mRNA of the full length leptin receptor OB R and of the short isoforms B219 . 1 B219 . 3 was identified in granulosa cells and the CL , as well as in the cortex and medulla . ^^^
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Dual labelling demonstrated widespread expression of the long form of the leptin receptor within all ORX cells that were examined . ^^^
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The secondary structure of leptin has similarities to the long chain helical cytokines family , which includes interleukin 6 ( IL 6 ) , IL 11 , CNTF , and LIF , and the leptin receptor is homologous to the gp 130 signal transducing subunit of the IL 6 type cytokine receptors . ^^^
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Pooling analysis of genetic data : the association of leptin receptor ( LEPR ) polymorphisms with variables related to human adiposity . ^^^ In the process of analyzing data pooled from nine studies on the human leptin receptor ( LEPR ) gene for the association of three alleles ( K109R , Q223R , and K656N ) of LEPR with body mass index ( BMI ; kilograms divided by the square of the height in meters ) and waist circumference ( WC ) , we encountered the following methodological challenges : data on relatives , missing data , multivariate analysis , multiallele analysis at multiple loci , heterogeneity , and epistasis . ^^^
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Cultured rat aortic VSMC expressed 130 kDa short form of leptin receptor . ^^^
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The obese gene product leptin is an important signaling protein that regulates food intake and body weight via activation of the hypothalamic leptin receptor ( Ob Rb ; Jacob et al . , 1997 ) . ^^^
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Although leptin has been shown to regulate Agrp / Npy and Pomc expressing neurones , there are differences with respect to Agrp regulation in leptin receptor deficient mice and rats . ^^^ Unlike the obese leptin receptor deficient db / db mouse , which exhibits upregulation of Agrp mRNA expression in the medial basal hypothalamus ( MBH ) compared to lean controls , the obese leptin receptor deficient ( faf ; Koletsky ) rat does not exhibit upregulation of Agrp expression . ^^^ To determine whether this represents a general difference between leptin receptor deficient mice and rats , neuropeptide gene expression was analysed in the MBH of lean and obese rats segregating for a different leptin receptor mutation , Leprfa ( Zucker ) . ^^^ By contrast , the absence of a functional leptin receptor results in the upregulation of Npy but not Agrp mRNA . . ^^^
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We report here the presence of leptin and leptin receptor mRNA in neonatal female rat brain and pituitary using RT PCR as well as leptin and leptin receptor immunoreactivity in neonatal rat brain . ^^^
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Hypothalamic leptin receptor ( OB Rb ) mRNA was significantly increased in both MAC 16 ( + 223 % ) and pair fed ( +192 % ) mice . ^^^
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The neuroprotective effect of leptin was antagonized both in vivo and in vitro by the Jak 2 inhibitor AG 490 , indicating that it was mediated via the leptin receptor and Jak 2 activation . ^^^
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Fever responses of Zucker rats with and without fatty mutation of the leptin receptor . ^^^ Zucker obese rats have a so called fatty mutation in the leptin receptor gene and express a dysfunctional protein . ^^^
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This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta 3 adrenergic receptor , tumor necrosis factor alpha , leptin , and leptin receptor ( Lepr ) in a cohort of Australian women . ^^^
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The present study was designed to ascertain whether 1 ) rat thyroid gland expresses the long form of leptin receptor ( ObRb ) and 2 ) the prolonged leptin administration ( daily subcutaneous injections of 24 nmol / kg leptin for 6 consecutive days ) affects thyroid gland function in this species . ^^^
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First , we have assessed the presence of the long isoform of the human leptin receptor by RT PCR . ^^^ We have found that leptin receptor , IRS 1 and the RNA binding protein Sam 68 are tyrosine phosphorylated upon leptin challenge in a dose dependent manner . ^^^ Finally , leptin receptor activation also triggers MAPK signaling pathway . ^^^ In summary , the present work demonstrates the presence of the long isoform of the human leptin receptor in peripheral blood mononuclear cells and the activation of two signaling pathways , PI3K and MAPK . ^^^
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The first experiment evaluated the anatomical distribution of leptin receptor mRNA in rat CBS using a sensitive fluorescence in situ hybridization method with a riboprobe specific for the long form of the leptin receptor ( Ob Rb ) . ^^^
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BACKGROUND : In fa / fa Zucker rats , leptin receptor deficiency is responsible for both a deficit of energy expenditure and hyperphagia which lead to massive obesity and insulin resistance in adulthood . ^^^
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The aims of this study were to examine whether this altered energy balance is associated with circulating leptin insufficiency , central leptin insensitivity , decreased hypothalamic leptin receptor ( Ob Rb ) expression , and / or increased hypothalamic neuropeptide Y ( NPY ) . ^^^
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Two color allele specific polymerase chain reaction ( PCR SSP ) assay of the leptin receptor gene ( Leprdb ) for genotyping mouse diabetes mutation . ^^^ An allele specific polymerase chain reaction ( PCR SSP ) assay for genotyping the mouse leptin receptor ( Leprdb ) mutation and its wild type ( Lepr+ ) gene was developed using two different fluorescent dye labeled primers . ^^^
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The kidney expresses abundant concentrations of the truncated isoform of the leptin receptor Ob Ra , but only a small amount of the full length receptor Ob Rb . ^^^
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Essentially identical results were obtained in db / db mice , which lack the expression of the long isoform of leptin receptor . ^^^ By RT PCR , we observed that B lymphocytes express leptin receptor mRNA , indicating that in addition to its effect on the cellular response , leptin may exert a direct effect on B cell function . ^^^
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Leptin receptor mRNA and immunoreactivity has been reported in various brain regions , while recent studies suggest that leptin is released from the human brain . ^^^
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Leptin is an adipocyte derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor ( OBR ) . ^^^ Although both leptin and OB R are expressed in pituitary cells , the mechanism of signal transduction and its regulation in this organ has not been studied extensively . ^^^
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Effect of tiangui recipe on expressions of hypothalamic leptin receptor and messenger ribonucleic acid of neuropeptide Y in androgen sterilized rats ] . ^^^ METHODS : In situs hybridization and autoradiography were adopted , using alpha 32 P radiolabelled leptin receptor ( OB R ) and neuropeptide Y ( NPY ) oligonucleotides probes and integrating with image pattern analysis , to observe the effect of TGR on changes of OB R , NPY mRNA expression in the hypothalamic arcuate nucleus ( ARC ) . ^^^
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The homozygous mutant Koletsky rat is a monogenic form of obesity and hyperphagia due to a null mutation of the leptin receptor ( lepr ( fak ) ) . ^^^ Corticotropin releasing factor decreases meal size by decreasing cluster number in Koletsky ( LA / N ) rats with and without a null mutation of the leptin receptor . ^^^
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However , this chronic low leptin signal is read differently from acute low leptin resulting from food deprivation ; leptin receptor gene expression in the hypothalamic arcuate nucleus ( ARC ) is lower in SD , whereas food deprivation increases expression levels , suggesting changes in sensitivity to leptin feedback . ^^^
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Leptin receptor signal transduction involves phosphorylation of cytosolic signal transducer and activator of transcription ( STAT ) proteins , specifically phosphorylation of STAT 3 ( P STAT 3 ) . ^^^
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Association of Gln223Arg variant in leptin receptor gene with metabolic abnormalities and hypertension in type 2 diabetes mellitus in Shanghai `` Han ' ' population ] . ^^^ OBJECTIVE : To investigate the association of Gln223Arg variant in leptin receptor gene with metabolic abnormalities and hypertension in type 2 diabetes mellitus . ^^^ METHODS : The genotypes of Gln223Arg variant in leptin receptor gene were determined by polymerase chain reaction restriction fragment length polymorphisms ( PCR RFLP ) assay in 359 unrelated subjects of Shanghai `` Han ' ' population ( including 193 subjects with normal glucose tolerance and 166 type 2 diabetic patients ) . ^^^ RESULTS : Significant difference of genotype frequency of Gln223Arg variant in leptin receptor gene was observed between hypertensive and normotensive type 2 diabetic male patients ( P = 0 . 008 ) . `` A ' ' allele was associated with increased systolic blood pressure ( P = 0 . 0026 ) and diastolic blood pressure ( P = 0 . 0084 ) in type 2 diabetic male patients . ^^^ CONCLUSION : Gln223Arg variant in leptin receptor gene is associated with hypertension in type 2 diabetic male patients , especially with elevation of systolic blood pressure . . ^^^
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The leptin receptor ( Ob R ) and the Janus kinase / signal transducer and activator of transcription ( JAK / STAT ) signaling pathway were evaluated by Western blot analysis . ^^^ SHR myocytes displayed similar Ob R protein abundance and basal NO levels , a blunted leptin induced increase in NOS activity as well as enhanced basal STAT 3 levels compared with the WKY group . ^^^
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Expression of the leptin receptor in rat and human nodose ganglion neurones . ^^^ Since cholecystokinin acts on vagal afferent neurones , we asked whether the leptin receptor was also expressed by these neurones . ^^^ Primers for different forms of the leptin receptor were used in reverse transcriptase polymerase chain reaction ( RT PCR ) of rat and human nodose ganglia . ^^^ RT PCR yielded products corresponding to the long ( functional ) form as well as short forms of the rat leptin receptor . ^^^ Moreover , RT PCR revealed the long form of the leptin receptor in a human nodose ganglion . ^^^
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No change was observed in leptin receptor levels in any region of the placentas from iron deficient dams . ^^^
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The mean level of leptin receptor ( OB R ) mRNA expression in the brain tissue and the mean level of long form type OB R ( OB RL ) mRNA expression in the hypothalamus of the OVX rats were significantly ( P < 0 . 05 ) lower than those in the SHAM group rats . ^^^ These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB R makes transmission of signals to suppress the amount of food intake difficult , thus leading to an increase in body weight . . ^^^
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In contrast , the expression of the full length leptin receptor ( ObRb ) was not affected by high fat feeding . ^^^
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Examples of such disorders of liporegulation include generalized lipodystrophies , mutations of leptin and leptin receptor genes , and diet induced obesity . ^^^
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Leptin upregulates beta 3 integrin expression and interleukin 1beta , upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures . ^^^ Human endometrium and endometrial epithelial cells ( EECs ) either cultured alone or cocultured with human embryos express leptin and leptin receptor . ^^^ We also determined the regulatory effects of IL 1beta on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell ( ESC ) cultures . ^^^ However , leptin exhibited marginal upregulation of leptin receptor . ^^^ The upregulation of beta 3 integrin and leptin / leptin receptor expression by IL 1beta in EEC cultures indicates that both cytokines may be implicated in embryonic maternal cross talk during the early phase of human implantation . ^^^
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The name `` leptin ' ' derived from the Greek word leptos , meaning `` thin . ' ' We hereby review major advances leading to our current finding of leptin , leptin receptor and its structure , the outline of homozygote , and also influence of leptin in the pituitary . ( The structure of leptin ) The mouse obese gene has been localized to chromosome 6 . ^^^ The resemblance of leptin precursor of human , mouse and rat is very high , i . e . , mouse and rat homology is 96 % and mouse and human homology is 83 % . ( The structure of leptin receptor ) The mutant gene , which is the cause of obesity , was shown on map on diabetic mouse ( db / db ) chromosome 4 , and it was proven to be the same as the leptin receptor gene cloned by Tartaglia et all . ^^^ The leptin receptor is glycoprotein consisting of a single transmembrane spanning component . ^^^ The primary structure of leptin receptor belongs to the cytokine class 1 family , the single membrane spanning receptor , and is highly related to the gp 130 signal transducing component of the interleukin 6 ( IL 6 ) receptor , the granulocyte colony stimulating factor ( G CSF ) receptor , and the leukemia inhibitory factor ( LIF ) receptor . ^^^ The leptin receptor is known to have at least six existing isoforms ( Ob Ra , b , c , d , e , f ) from the difference in splicing . ( Homozygote Mutation of Leptin and Leptin Receptor : Hormone Secretion Disorders ) The point mutation of ob / ob mouse and the splicing mutation of db / db mouse show remarkable obesity and hyperphagia . ^^^
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Leptin and leptin receptor in anterior pituitary function . ^^^ Leptin is a 16 kDa protein that exerts important effects on the regulation of food intake and energy expenditure by interacting with the leptin receptor in the brain and in many other tissues . ^^^ Many studies have implicated leptin in anterior pituitary function including the observation that homozygous mutations of the leptin receptor gene led to morbid obesity , lack of pubertal development and decreased GH and TSH secretion . ^^^ All of the anterior pituitary cell types express the leptin receptor . ^^^
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We investigated the presence and pattern of distribution of leptin mRNA and the mRNA of the long isoform of the leptin receptor in the normal pituitary and in different types of pituitary adenomas . ^^^ The leptin receptor long isoform was detected in the majority ( 65 % ) of pituitary tumors and in all normal pituitaries . ^^^
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Leptin receptor has homology to members of class 1 cytokine receptor family , which may imply similarities in molecular events engaged by cytokines and leptin . ^^^ Leptin receptor isoforms , long signaling and short nonsignaling , have been recently localized in human pituitaries . ^^^
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The effects of leptin on hypothalamic , pituitary and peripheral hormone levels , as well as the presence of the leptin receptor in a variety of tissues , suggest both an endocrine and a paracrine mode of action . ^^^ Particular attention was paid to the effect of leptin on the gonadal axis as infertility , a characteristic feature of both the leptin deficient ob / ob mice and the leptin receptor mutant db / db mice , could be corrected in ob / ob mice by leptin administration . ^^^
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GH treatment has been shown to reduce serum leptin ; however , the physiological interactions between the leptin system ( free leptin , bound leptin , and soluble leptin receptor ) and the GH / IGF 1 system largely remain unknown . ^^^ The following parameters were recorded at baseline ( V 1 ) and then after 3 months ( V 2 ) and 6 months ( V 3 ) on GH treatment : fat mass , body mass index ( BMI ) , and waist / hip ratio ( WHR ) ; blood samples were taken after an overnight fast for free leptin , bound leptin , soluble leptin receptor , insulin , and IGF 1 . ^^^ Simultaneously , there was a rise in insulin ( P = 0 . 068 and P < 0 . 001 ) , IGF 1 ( P < 0 . 001 and P < 0 . 001 ) , bound leptin ( P = 0 . 005 and P < 0 . 001 ) , and soluble leptin receptor ( P = 0 . 61 and P < 0 . 001 ) . ^^^ Soluble leptin receptor was also positively related to IGF 1 ( P < 0 . 001 ) . ^^^ However , the observed changes in free leptin and bound leptin and , more importantly , the rise in soluble leptin receptor , are not explained entirely by modifications in body composition and may be a direct result of GH / IGF I . . ^^^
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Leptin receptor expression in nodose ganglion cells projecting to the rat gastric fundus . ^^^ In order to assess the possible role of vagal afferent neurons in transmitting leptin signals from the stomach to the brain , leptin receptor ( OB R ) expression was investigated in rat nodose ganglion cells and their projection to the stomach determined by retrograde tracing . ^^^
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Obesity induced by abnormality in leptin receptor and melanocortin 4 receptor ] . ^^^ In this paper , we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin 4 receptor . . ^^^
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Using double label in situ hybridization , we found that nearly all ( 98 % ) GALP mRNA expressing cells in the arcuate nucleus also express mRNA for the long form of the leptin receptor . ^^^
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The recombinant chicken leptin markedly inhibits food intake as reported in mammals , suggesting the presence of an hypothalamic leptin receptor . ^^^ The chicken leptin receptor has been identified and all functional motifs are highly conserved compared to mammalian homologous . ^^^ Chicken leptin receptor is expressed in the hypothalamus but also in other tissues such as pancreas , where leptin inhibits insulin secretion and thus may have a key role in regulating nutrient utilization in this species . . ^^^
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Because these obesity and diabetes syndromes reflect different collections of QTL , rather than null mutations in the leptin or leptin receptor genes , they are extremely relevant as models for the polygenic obesity / diabesity syndromes in humans . . ^^^
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Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity . ^^^ The mechanisms underlying this leptin resistance are unknown , but may involve reduced leptin transport across the blood brain barrier via short isoforms of the leptin receptor ( Ob R ) . ^^^ Second , brain uptake of leptin was reduced in mice lacking Ob R . ^^^ These data support the ideas that short isoforms of Ob R are involved in brain uptake of leptin and that impaired blood brain barrier function contributes to the pathogenesis of obesity . ^^^
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Resting metabolic rate , plasma leptin concentrations , leptin receptor expression , and adipose tissue measured by whole body magnetic resonance imaging in women with Prader Willi syndrome . ^^^ We also examined leptin receptor expression in the PWS group . ^^^ Messenger RNA expression of the leptin receptor was examined by reverse transcriptase polymerase chain reaction in lymphocytes . ^^^ Full length leptin receptor messenger RNA was expressed in the lymphocytes of the PWS group . ^^^ There is no evidence that defective leptin production causes obesity in PWS , and leptin receptor deficiency is not a primary consequence of the gene defects leading to leptin resistance . . ^^^
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Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species , including sheep . ^^^ Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species , including cattle . ^^^ Leptin receptor mRNA is also found in the testes of rodents . ^^^
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The porcine leptin receptor has been cloned and is a member of the class 1 cytokine family of receptors . ^^^ The leptin receptor is localized in the brain and pituitary of the pig . ^^^
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OBJECTIVE : To determine whether the blood concentrations of leptin and soluble leptin receptor ( LEPR ) hang in women after bilateral ovariectomy , and whether there is a relationship between the concentrations of leptin , LEPR and LH , FSH and 17 beta estradiol before and after castration . ^^^ RESULTS : We did not find any statistically significant changes in the concentration of leptin ( 8 . 9 + / 5 . 5 vs 7 + / 5 . 6 ) and LEPR ( 16 . 2 + / 5 . 6 vs 20 . 9 + / 8 . 9 ) before and after surgical castration . ^^^ Five days after surgical castration we found only a tendency toward decrease in the concentration of leptin and an increase in the LEPR concentration . ^^^ Except for the positive correlation between leptin concentration and BMI , we did not find any statistically significant correlation between the concentrations of leptin and LEPR and any of the other evaluated parameters in both groups . ^^^ There was a tendency toward a decrease in serum concentrations of leptin and increase in serum concentration of LEPR after surgery , but it was not statistically significant , which is in contrast to another study published regarding this topic . . ^^^
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In contrast , the leptin receptor with intracytoplasmic signal sequence was detected in the follicular papilla cells immunohistochemically , and the long isoform of the leptin receptor mRNA was demonstrated in the human follicular papilla cell lines by reverse transcription polymerase chain reaction . ^^^ These data demonstrated that human follicular papilla cells produce leptin and express the functional leptin receptor in vivo and in vitro , suggesting its autocrine function . ^^^
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These data , compared with published data on leptin receptor gene expression , provide evidence that leptin could be produced by different cell types of the mammary gland and could act as a paracrine factor on mammary cell growth and differentiation via adipose epithelial cells and myoepithelial epithelial cell interactions . . ^^^
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Soluble leptin receptor and insulin resistance as determinant of sleep apnea . ^^^ MEASUREMENTS : Insulin action and plasma soluble leptin receptor were measured by euglycemic hyperinsulinemic glucose clamp and by ELISA method , respectively . ^^^ RESULTS : The apnea / hypopnea index ( AHI ) was positively correlated with plasma soluble leptin receptor ( 0 . 76 ; P < 0 . 001 ) and negatively with the degree of insulin mediated glucose uptake ( r= 0 . 73 ; P < 0 . 001 ) . ^^^ In a multivariate analysis AHI was associated with plasma soluble leptin receptor and insulin mediated glucose uptake independently of age , gender , BMI , plasma leptin levels and PaCO ( 2 ) . ^^^ CONCLUSION : Sleep apnea syndrome is associated with plasma soluble leptin receptor and insulin resistance independently of BMI . . ^^^
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Thus leptin appears to act as a modulator of sweet taste , provided a functional leptin receptor is expressed by the taste cells . ^^^
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In this context , testicular expression of leptin receptor ( Ob R ) gene shows a complex pattern of alternative splicing with generation of multiple variants , including the functional leptin receptor type b ( Ob Rb ) and several short isoforms . ^^^ Moreover , Ob R mRNA expression in rat testis was regulated by homologous ( leptin ) as well as heterologous ( gonadotropins ) signals . ^^^
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Our results showed the expression of both leptin receptor transcripts in all tumoral tissues examined . ^^^
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Leptin is a 16 kd hormone that mediates a range of metabolic effects by using a transduction pathway from the long form of the leptin receptor , OB R ( L , ) through Janus kinase signal transducer and activator of transcription ( Jak Stat ) signaling components . ^^^ Leptin is produced by hepatic stellate cells ( HSCs ) but only following their `` activation . ' ' Because activation of stellate cells is a central event in the fibrotic response to liver injury , we hypothesized that leptin may directly stimulate fibrogenesis in activated stellate cells via OB R ( L ) . ^^^
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Two predominant splice variants of the leptin receptor ( LEPR ) are coexpressed in leptin responsive tissues : the long form , LEPRb , characterized as the signal transducing receptor , and the signaling defective short form , LEPRa . ^^^ Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase / signal transducer and activator of transcription activation by receptor heterodimers . ^^^
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In humans , mutations in leptin , leptin receptor , proopiomelanocortin ( POMC ) , melanocortin 4 receptor ( MC4R ) and prohormone convertase 1 ( PC 1 ) have been described in patients with severe obesity . ^^^
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OBJECTIVE : To test the hypothesis that leptin contributes to in vivo thrombosis via the leptin receptor . ^^^ DESIGN AND MATERIALS : Between September 2000 and September 2001 , a vascular thrombosis model was used to test male 10 to 12 week old mice completely deficient in leptin or the leptin receptor and mice with platelet leptin receptor deficiency . ^^^ RESULTS : Following onset of vascular injury , wild type mice ( n = 8 ) formed occlusive thrombosis in a mean ( SD ) of 42 . 2 ( 4 . 6 ) minutes , whereas leptin deficient ( n = 5 ) and leptin receptor deficient mice ( n = 7 ) formed occlusive thrombosis in 75 . 2 ( 10 . 1 ) and 68 . 6 ( 10 . 3 ) minutes , respectively ( leptin deficient vs wild type mice , P = . 008 ; leptin receptor deficient vs wild type , P = . 03 ) . ^^^ Following bone marrow transplantation from leptin receptor deficient ( donor ) mice to wild type ( recipient ) mice , the time to occlusion was prolonged from 22 . 3 ( 2 . 8 ) minutes in wild type mice receiving wild type marrow ( n = 3 ) to 56 . 8 ( 5 . 0 ) minutes in wild type mice receiving leptin receptor deficient bone marrow ( n = 5 ) ( P = . 003 ) . ^^^ CONCLUSIONS : Leptin contributes to arterial thrombosis following vascular injury in vivo and these prothrombotic effects appear to be mediated through the platelet leptin receptor . . ^^^
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Defects in the leptin gene or the leptin receptor may be a genetic cause of obesity , but little is known about the familial associations of leptin and obesity . ^^^
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Leptin and soluble leptin receptor levels in obese and weight losing individuals . ^^^ To investigate soluble leptin receptor ( sLR ) in plasma , specific anti sLR monoclonal antibodies were developed . ^^^
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Circulating concentrations of soluble leptin receptor : influence of menstrual cycle and diet therapy . ^^^ Concentrations of the soluble leptin receptor ( sOB R ) may be related to leptin resistance in obesity . ^^^ The reduction in serum sOB R concentrations in overweight and obese persons may reflect downregulation of hypothalamic leptin receptor production as a result of an increase in circulating leptin and might be an important factor in leptin resistance . . ^^^
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This leptin induced ET 1 expression was inhibited by preincubation of HUVECs with 0 . 75 micromol / L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob Rb . ^^^
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Leptin receptor gene expression in these acini was significantly increased by caerulein and leptin . ^^^ We conclude that 1 / central or peripheral pretreatment with leptin protects the pancreas against its damage induced by CIP , whereas melatonin exerts its protective effect only when given i . p . , but not following its i . c . v . adminstration , 2 / activation of leptin receptor in the pancreatic acini appears to be involved in the beneficial effects of leptin on acute pancreatitis , 3 / the protective effects of leptin involve sensory nerves , CGRP and increased generation of NO whereas melatonin induced protection of the pancreas depends mainly on the antioxidant local effect of this indole , and scavenging of the radical oxygen species in the pancreatic tissue . . ^^^
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These effects were found to be inhibited by phosphatidylinositol 3 kinase inhibitors , absent in muscles from obese Lepr ( db ) mice which have the dysfunctional long form of leptin receptor , and blunted in muscles from diet induced obese mice in the fed state but not during fasting . ^^^
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R128Q mutations did not change the binding properties to BAF / 3 cells stably transfected with the long form of human leptin receptor compared , respectively , to non mutated human , ovine , and chicken leptins . ^^^ If dimerization models were applicable leptin receptor activation , the present results would suggest that site 2 of the hormone was impaired . ^^^
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Luteinized GC were also counted for cell number and detected the expression of the leptin receptor by reverse transcription polymerase chain reaction analysis . ^^^ The leptin receptor expression was demonstrated in luteinized GC . ^^^ CONCLUSIONS : Leptin may directly attenuate the IGF 1 or IGF 1 and FSH stimulated E ( 2 ) synthesis in cultured human luteinized GC by the leptin receptor mechanism . . ^^^
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This attenuation , downstream of the leptin receptor , may be contributing to the leptin resistance and age related weight gain in these aged obese rats . ^^^
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The aim of this study was to investigate the expression of leptin and its receptor ( OB R ) in mouse oocyte and preimplantation embryo , and to examine whether leptin influenced the early embryo development . ^^^ Leptin mRNA was detected in blastocyst and hatched blastocyst , and two splice variants of OB R ( OB Ra and OB Rb ) mRNAs were detected in oocytes , 1 cell , 2 cell , morula , blastocyst , and hatched blastocyst . ^^^
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Finally , an association between CH and severe obesity has been described in patients with leptin receptor ( Leptin R ) mutations . ^^^
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The overall expression of leptin receptors was increased while the expression of the physiologically active long form of leptin receptor was decreased in the hypothalamus and the perigonadal fat of ethanol consuming mice . ^^^ Ethanol consumption also decreased hypothalamic expression of STAT 3 , a protein associated with leptin receptor activation in this region of the brain . ^^^ In contrast , STAT 1 , a protein associated with leptin receptor activation in adipose tissue , was significantly elevated in the perigonadal fat of ethanol consuming mice . ^^^
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Leptin receptor was also expressed in all of the main ovarian cell types , with the thecal cell layer exhibiting the highest staining levels . ^^^
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In transfection studies , PTP1B dephosphorylates the leptin receptor associated kinase , Jak 2 . ^^^
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Reverse transcriptase polymerase chain reaction ( RT PCR ) analysis of RNA showed that L 6 muscle cells express a short isoform of the leptin receptor ( ObRa ) , but not the long isoform ( ObRb ) . ^^^ The results suggest that leptin can act directly on L 6 muscle cellsvia a short leptin receptor isoform to acutely stimulate basal ( but not insulin stimulated ) glucose uptake via a PI3K dependent pathway . . ^^^
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Hypothalamic gene expression in sheep for cocaine and amphetamine regulated transcript , pro opiomelanocortin , neuropeptide Y , agouti related peptide and leptin receptor and responses to negative energy balance . ^^^ We then examined in adult male castrated sheep the effects of acute negative energy balance induced by a 4 day fast on the amounts of these mRNAs and those for leptin receptor ( OB Rb ) , neuropeptide Y ( NPY ) and pro opiomelanocortin ( POMC ) . ^^^
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In conclusion , the neuronal , perinuclear localization of leptin IR in rat brain corresponds closely to that of leptin receptor ( OB R ) IR , which has also been detected intracellularly . ^^^ Our observation of leptin IR associated with cell nuclei suggests the existence of an OB R distinct from the well described membrane forms . . ^^^
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Leptin acts on the hypothalamus to reduce food intake and on a number of non neuronal tissues via specific receptors ( Lepr ) . ^^^ Embryonic expression of the leptin receptor gene in mesoderm derived tissues . ^^^
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Distribution of the long leptin receptor isoform in brush border , basolateral membrane , and cytoplasm of enterocytes . ^^^ Recent studies have demonstrated leptin and leptin receptor expression in gastric epithelial cells . ^^^ In the present study , we report the presence of the long leptin receptor isoform ( OB Rb ) in human , rat , and mouse small intestine , supporting the hypothesis of leptin as a hormone involved in gastrointestinal function . ^^^ METHODS : The presence of the leptin receptor was determined by immunocytochemical methods using antibodies against the peptide corresponding to the carboxy terminus of the long isoform of the leptin receptor . ^^^ RESULTS : Immunoreactivity for the long leptin receptor isoform was observed in the three studied species . ^^^
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Plasma leptin binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat . ^^^ In the present study , we assessed whether this apparent leptin resistance during rat pregnancy was due to either increased plasma leptin binding activity and / or reduced expression of hypothalamic leptin receptor . ^^^ Hypothalamic expression of mRNA encoding the long form of the leptin receptor ( Ob Rb ) was elevated in early pregnancy ( Day 7 ) but returned to prepregnancy levels by midgestation and remained stable thereafter . ^^^
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Mutations in the human leptin and leptin receptor genes as models of serum leptin receptor regulation . ^^^ These data demonstrate that leptin is not needed for ObR gene expression , and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects , whereas sObR levels are not depressed in obese leptin deficient or leptin receptor deficient individuals . . ^^^ Immunoreactive sObR was measured in 125 lean or obese control subjects ( group 1 ) , 18 individuals with a mutation in the leptin gene impairing leptin secretion ( group 2 ) , and 10 individuals with a mutation in the ObR gene , leading to production of a truncated ObR not anchored to cell membranes ( group 3 ) . ^^^ A part of serum Ob leptin , an adipocyte secreted peptide , is bound to a soluble Ob receptor ( sObR ) . ^^^
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A meta analytic investigation of linkage and association of common leptin receptor ( LEPR ) polymorphisms with body mass index and waist circumference . ^^^ METHODS : We analyzed data pooled from nine studies on the human leptin receptor ( LEPR ) gene for the association of three alleles ( K109R , Q223R and K656N ) of LEPR with body mass index ( BMI ; kg / m ( 2 ) ) and waist circumference ( WC ) . ^^^
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While cells transfected with the signalling competent long form of the leptin receptor ( ObRb ) have been used to study leptin signalling , these are likely to be of limited use in studying STAT 3 Ser727 phosphorylation due to the importance of cell background in determining the nature of the response . ^^^
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Quantification of the soluble leptin receptor in human blood by ligand mediated immunofunctional assay . ^^^ Panels of monoclonal antibodies ( mAbs ) were raised against recombinant human leptin and the recombinant human soluble leptin receptor . ^^^ Using these mAbs , we established a ligand mediated immunofunctional assay ( LIFA ) to quantify concentrations of the soluble leptin receptor , which has been shown to be a major binding protein for leptin in human serum . ^^^ In performing the assay , a monoclonal antibody ( mAb 2H6 ) against the soluble leptin receptor , which binds an epitope outside the leptin binding site and equally recognizes both , free and leptin occupied soluble leptin receptor , is used to capture the soluble leptin receptor on a microtiter plate . ^^^ Recombinant human leptin is added to saturate all binding sites , and a biotinylated anti leptin mAb ( 4D3 ) detects the amount of leptin ( endogenous and exogenous ) bound to the soluble leptin receptor . ^^^
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Expression of the long ( OB RB ) and short ( OB RA ) forms of the leptin receptor throughout the oestrous cycle in the mature rat ovary . ^^^ Leptin is secreted by adipocytes and exerts its effects by interacting with the long form of the leptin receptor , OB RB . ^^^ It was hypothesized that expression of the leptin receptor gene varies throughout the oestrous cycle to modulate the sensitivity of the ovary to leptin . ^^^ In this study , expression of genes for the long and short isoforms of the leptin receptor in the adult ovary was investigated at different stages of the rat oestrous cycle . ^^^ Ovaries were collected and RNA was extracted for real time RT PCR analysis of leptin receptor gene expression . ^^^
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Furthermore , hOBs and osteosarcoma cell lines expressed the long signal transducing form of the leptin receptor ( OB Rb ) as shown by RT PCR . ^^^
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Day 20 placentas from viable foetuses were examined for immunoexpression of ( a ) cytokines : tumour necrosis factor alpha ( TNF alpha ) , TNFR 1 receptor ( p 55 ) , leptin and leptin receptor , ( b ) apoptosis : TdT mediated dUTP nick end labelling ( TUNEL ) positive cells , bax and bcl 2 . ^^^
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Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans . ^^^ One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin . ^^^ In the present study , we measured the soluble leptin receptor ( SLR ) levels in lean and obese humans . ^^^ MEASUREMENTS : A direct double monoclonal sandwich enzyme linked immunosorbent assay ( ELISA ) was used for the quantitative measurement of the soluble human leptin receptor . ^^^ CONCLUSION : Obesity , in humans is associated with decreasing levels of the circulating soluble leptin receptor ( SLR ) . ^^^
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In addition , we investigated possible molecular mechanisms responsible for the lower leptin levels in hHTg rats by measuring leptin and leptin receptor ( Ob Ra ) mRNA levels . ^^^
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Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal ( mutations of the leptin gene or of the leptin receptor gene ) , which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake . . ^^^
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Regulation of circulating soluble leptin receptor levels by gender , adiposity , sex steroids , and leptin : observational and interventional studies in humans . ^^^ A circulating soluble form of the leptin receptor [ soluble leptin receptor ( sOB R ) ] is the main leptin binding protein and determinant of free leptin index ( FLI ) , the presumed biologically active form of leptin . ^^^ A 72 h fast in eight men decreased leptin levels by 80 % and increased lymphocyte expression of leptin receptor mRNA and serum sOB R levels by 100 % . ^^^
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In humans , mutations in the genes encoding leptin and the leptin receptor result in obesity syndromes and hypogonadotropic hypogonadism . 1 have shown that administration of recombinant human leptin results in the onset of puberty at an appropriate developmental age in human congenital leptin deficiency . ^^^
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Although the effects of leptin have been more thoroughly documented in nonprimate species than in primates , a few human families with genetic mutations of the gene for leptin or the leptin receptor show obesity and impaired fertility . ^^^
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Antibodies to the leptin receptor were used to identify binding sites in adult lung and isolated fetal lung type 2 cells . ^^^
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To clarify whether obesity per se leads to increased prevalence of cholelithiasis , we examined cholesterol gallstone susceptibility in three polygenic ( KK / H1J , NON / LtJ , NOD / LtJ ) and five monogenic [ carboxypeptidase E ( Cpe ( fat ) ) , agouti yellow ( A ( y ) ) , tubby ( tub ) , leptin ( Lep ( ob ) ) , leptin receptor ( Lepr ( db ) ) ] murine models of obesity during ingestion of a lithogenic diet containing dairy fat , cholesterol , and cholic acid . ^^^ Dysfunction of the leptin axis , as evidenced by the Lep ( ob ) and the Lepr ( db ) mutations , markedly reduced gallstone formation in a genetically susceptible background strain , indicating that in mice with this genetic background , physiologic leptin homeostasis is a requisite for cholesterol cholelithogenesis . ^^^
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Leptin receptor ( Ob R ) expression is induced in peripheral blood mononuclear cells by in vitro activation and in vivo in HIV infected patients . ^^^ These effects are mediated by the long isoform of the leptin receptor , which has been shown to trigger signalling in PBMC . ^^^ In order to assess possible regulation of the long isoform of the leptin receptor ( Ob R ) in mononuclear cells upon activation , we have studied the expression of Ob R by RT PCR and Western blotting in PBMC activated in vitro by PHA or ConA and in vivo in HIV infected patients . ^^^ We have found that in vitro activation and in vivo HIV infection correlates with an increase in leptin receptor expression in PBMC . ^^^ Moreover , the leptin receptor is tyrosine phosphorylated in PBMC from HIV infected patients , suggesting that the leptin receptor is activated . ^^^
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Weight loss increases soluble leptin receptor levels and the soluble receptor bound fraction of leptin . ^^^ OBJECTIVE : Soluble leptin receptor ( sOB R ) represents the main binding site for leptin in human blood . ^^^ The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound / free ratio after pronounced weight reduction . ^^^
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They underwent clinical examination and assessment of plasma or serum levels of ghrelin leptin , soluble leptin receptor , IGF 1 , IGFBP 1 and IGFBP 3 . ^^^
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The growth hormone secretagogue ( GHS ) ghrelin is known to stimulate food intake and to be the endogenous ligand for the GHS receptor , which is strongly expressed in the arcuate nucleus , like the leptin receptor ( Ob R ) . ^^^
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The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied . ^^^ Food restriction in old rats lowered adiposity and serum leptin to values close to those of young rats , recovered responsiveness to i . c . v . administration of leptin at the dose of 0 . 2 microg / day and increased leptin receptor expression in the hypothalamus . ^^^ Food restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing . . ^^^
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Polar expression and phosphorylation of human leptin receptor isoforms in paired , syncytial , microvillous and basal membranes from human term placenta . ^^^
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Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum . ^^^
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The effect depends on intact and functional leptin receptors because it occurs neither in rats with a leptin receptor defect nor in rats with acquired leptin resistance . . ^^^
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However , the mechanisms could not be explained in most cases of human obesity , except for rare cases with mutations in the leptin receptor . ^^^ In this study , we examined the effects of ethanol on the leptin induced JAK / STAT signaling pathway using human hepatoma cell lines transiently expressing long form of the leptin receptor . ^^^
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CONCLUSION : Our findings suggest that genetic variability in the leptin receptor and neuropeptide Y genes is implicated in body weight regulation , the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian population , especially in non smokers , while the NPY Leu7Pro polymorphism was associated with BMI reduction in premenopausal women . . ^^^
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Regulation of Jak kinases by intracellular leptin receptor sequences . ^^^ Leptin signals the status of body energy stores via the leptin receptor ( LR ) , a member of the Type 1 cytokine receptor family . ^^^
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Discovery of the leptin receptor and its downstream peptidergic pathways has reconfirmed the crucial role of the hypothalamus in the regulation of food intake and energy balance . ^^^
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Comparing mRNA levels of genes encoding leptin , leptin receptor , and lipoprotein lipase between dairy and beef cattle . ^^^ The aim of this study was to determine whether the expression of the obese ( Ob ) gene and lipoprotein lipase ( LPL ) gene in fat tissues and expression of the long isoform leptin receptor ( Ob Rb ) gene in the hypothalamus were different between these two cattle breeds . ^^^
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These effects were suggested to be mediated through the hypothalamic center via the Ob Rb receptor ( long isoform of leptin receptor ) . ^^^ Although short isoforms of leptin receptor exist in many regions of the brain , there has been little in vivo functional study of these areas such as for leptin ' s target site . ^^^
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A subdomain of the human leptin receptor encoding part of the extracellular domain ( amino acids 428 to 635 ) was subcloned , expressed in a prokaryotic host , and purified to homogeneity , as evidenced by SDS PAGE , with over 95 % monomeric protein . ^^^ LBD blocked leptin induced , but not interleukin 3 induced , proliferation of BAF / 3 cells stably transfected with the long form of human leptin receptor . ^^^
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The aim of this study was to determine the effect of the leptin receptor mutation in the Zucker rat on gastric leptin production and on the response to 14 hours of starvation . ^^^ However , there is still an effect of the nutritional status on gastric leptin levels despite the lack of a functional leptin receptor . . ^^^
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Leptin transport across the blood brain barrier of the Koletsky rat is not mediated by a product of the leptin receptor gene . ^^^ It has been assumed that the short form of the leptin receptor , which is a splice variant of the gene which produces all known leptin receptors , is the leptin transporter , but evidence for this is mixed . ^^^
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Leptin and leptin receptor ] . ^^^
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Leptin had no effect on weight gain or food intake of C57BL / 3J db / db mice , which only express the soluble leptin receptor . ^^^
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Generation of soluble leptin receptor by ectodomain shedding of membrane spanning receptors in vitro and in vivo . ^^^ Genetically obese rodents with mutations of leptin or leptin receptor develop morbid obesity and diabetes . ^^^ However , soluble leptin receptor does circulate in human plasma and represents the major leptin binding activity . ^^^ In this report , we attempted to determine whether the soluble leptin receptor may also be derived from membrane spanning receptor isoforms by ectodomain shedding . ^^^ Using stable cell lines expressing both OB Ra , the most abundant leptin receptor isoform , and OB Rb , the signaling form of the leptin receptor , we demonstrate that soluble leptin receptor protein can indeed be generated by proteolytic cleavage of these two receptor isoforms in vitro . ^^^
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Leptin receptor isoform expression in rat osteoblasts and their functional analysis . ^^^
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Leptin receptor expression in the rat placenta : changes in ob ra , ob rb , and ob re with gestational age and suppression by glucocorticoids . ^^^ Because glucocorticoids inhibit feto placental growth , placental leptin receptor ( Ob R ) expression was also measured after manipulation of feto placental glucocorticoid exposure . ^^^
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The expression of leptin receptor isoforms was evaluated by reverse transcriptase polymerase chain reaction ( RT PCR ) in cells obtained from five adenomas . ^^^
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Since leptin is one of the primary hormones involved in the regulation of body weight and energy homeostasis , we investigated whether PTP1B affects leptin receptor ( lepR ) signaling directly . ^^^
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The purpose of this study was to identify the leptin receptor and to determine the effects of leptin on type 1 collagen expression in the human stellate cell line , LX 1 . ^^^ The leptin receptor ( OB R ) was demonstrated by immunofluorescent staining and confocal microscopy . ^^^ However , only the short forms ( Ob R ( s ) ) , but not the long forms ( Ob R ( l ) ) , of leptin receptor mRNA expression were detected . ^^^
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Circulating soluble leptin receptor and free leptin index during childhood , puberty , and adolescence . ^^^ Leptin is bound in human blood by a high affinity binding protein , which appears to be identical with the soluble leptin receptor ( sOB R ) . ^^^
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In experiment 2 , ob / ob mice , wild type mice , and two db / db mutants , C57BL / 6J db ( Lepr ) / db ( Lepr ) ( BL / 6J ) mice possessing short form and circulating leptin receptors and C57BL / 6J db ( 3J ) / db ( 3J ) ( BL / 3J ) mice expressing only circulating receptors , were lipectomized or sham operated . ^^^
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The efficiency of leptin itself or of small molecule agonists of the leptin receptor should be studied in relation with genetic variations in the leptin gene promoter . ^^^
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Leptin receptor ( Ob Rb ) was higher in the ARC under LD . ^^^
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We studied rats with transplanted AML to test if a neutralizing anti leptin receptor monoclonal antibody ( mAb ) ( anti OB R ) could inhibit leukemogenesis . ^^^ We could not detect surface expression of the leptin receptor on the leukemic cells , but on mononuclear cells from healthy rats . ^^^ The anti OB R had no effect on either leukemic cell growth or angiogenesis in leukemic fa / fa rats with a mutated leptin receptor . ^^^
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Western blotting revealed that the transcripts were translated into 16 kDa leptin , and 125 kDa ( long ) and 100 kDa ( short ) leptin receptor isoforms . ^^^
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Increased bone mass has been linked to the absence of leptin and leptin receptor signaling in ob / ob and db / db mice . ^^^
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Leptin was measured using a modified culture of HEK 293 cells , expressing both the human leptin receptor gene and the firefly luciferase gene driven by a STAT inducible promoter . ^^^ Relatively high levels of leptin activity ( 50 250 ng / ml ) were detected in wound fluids using the leptin receptor expressing HEK 293 cells . ^^^
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Moreover IFN gamma increased the expression of the functional form of leptin receptor ( Ob Rb ) and this effect was potentiated by leptin in a concentration dependent manner . 6 . ^^^
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Impaired natural killer ( NK ) cell activity in leptin receptor deficient mice : leptin as a critical regulator in NK cell development and activation . ^^^ Leptin is an adipocyte secreted hormone that centrally regulates weight control via targeting the leptin receptor in the central nervous system . ^^^ Recently , the leptin receptor has also been detected in peripheral systems including immune tissues , suggesting that leptin may play an important role in the regulation of immune function . ^^^ In the present paper , we observed that percentage of NK cells and total amount of NK cells in the liver , spleen , lung , and peripheral blood were declined in leptin receptor deficient mice ( db / db B 6 mice ) , indicating that NK cell development was vigorously influenced by leptin receptor deficiency . ^^^
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We have systematically examined the distribution of leptin receptor containing neurons in the porcine hypothalamus by means of immunohistochemical staining methods . ^^^ Leptin receptor immunoreactivity ( OBR IR ) was observed in both the preoptic area and anterior hypothalamic area . ^^^
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Analyses of serum leptin and free leptin receptor in the serum of patients with steatosis showed significant variations from reference limits of normal values . ^^^ The results obtained from analysis of serum leptin and free leptin receptor in the serum are presented and evaluated . ^^^
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Different isoforms of the soluble leptin receptor in non pregnant and pregnant mice . ^^^ As shown in humans , a soluble leptin receptor ( sOB R ) , which modulates the effects of its ligand , circulates in murine blood . ^^^
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Nutritional regulation of hypothalamic leptin receptor gene expression is defective in diet induced obesity . ^^^ Although the mechanism of leptin resistance is not clearly understood , alterations in leptin receptor ( Ob R ) gene expression have been proposed as a potential mechanism mediating modifications in leptin action in obesity and during changes in nutritional status ( fed / fasted ) . ^^^ To address the possibility that elevated leptin concentration in DIO rats may mediate an alteration in OB R mRNA levels , we examined the effects of adenovirus mediated hyperleptinaemia on Ob R gene expression in SC rats . ^^^ Despite substantially elevated plasma and cerebrospinal fluid concentrations of leptin , hypothalamic Ob R mRNA levels were similar in both groups . ^^^
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Leptin receptor and STAT 3 , a transcription factor mediating the leptin signaling , are distributed in the widespread brain regions including the cerebral neocortex , hippocampal formation and lower brainstem as well as the hypothalamus where MCH fibers and the MCH receptor are abundantly present . ^^^ These findings suggest that MCH exerts the effect through its specific receptor distributed throughout the brain and that the function of MCH is influenced by the condition of peripheral energy balance via leptin , the leptin receptor and STAT 3 , not only in the hypothalamus , but also in other brain regions . ^^^
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We now demonstrate that the activation of the IL 1Ra promoter by leptin is strictly dependent on the presence of the long form of the leptin receptor ( OB Rb ) , and that it also requires the activation of the p42 / 44 mitogen activated protein kinases ( MAPKs ) as well as the presence of a nuclear factor kappaB ( NF kappa B ) / PU . 1 composite site at position 80 of the IL 1Ra promoter . ^^^
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To elucidate the importance of the leptin regulatory feedback loop in the genetic changes produced by this selection , Lep ( ob ) and Lepr ( db ) mutations causing leptin production and leptin receptor deficiency , respectively , were introgressed individually into both lines by repeated backcrossing . ^^^
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Based on in vitro and ex vivo studies , protein tyrosine phosphatase 1B ( PTP1B ) was implicated in the regulation of several RTKs , yet mice lacking PTP1B show defects mainly in insulin and leptin receptor signaling . ^^^
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Gene expression ( measured by in situ hybridisation ) in the hypothalamic arcuate nucleus ( ARC ) was higher in LBC than HBC sheep for neuropeptide Y ( NPY ; 486 % of HBC , P < 0 . 01 ) , agouti related peptide ( AGRP ; 467 % , P < 0 . 05 ) and leptin receptor ( OB Rb ; 141 % , P < 0 . 05 ) , but lower for cocaine and amphetamine regulated transcript ( CART ; 92 % , P < 0 . 05 ) and similar between groups for pro opiomelanocortin ( POMC ) . ^^^
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Leptin ( > 10 ( 11 ) m ) increased proliferation of isolated fetal rat osteoblasts comparably with IGF 1 , and these cells expressed the signalling form of the leptin receptor . ^^^ Leptin stimulated proliferation of isolated chondrocytes , and these cells also expressed the signalling form of the leptin receptor . ^^^
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The discoveries of expression of leptin receptor isotypes in a wide range of tissues in the body have encouraged investigation of leptin interactions in the periphery . ^^^
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In addition , a leptin receptor has been detected in taste cells of mouse circumvallate papillae and in rat intestinal epithelium . ^^^ The results show that intralobular duct cells of submandibular and parotid glands are immunoreactive for leptin , leptin receptor and glucagon but not for insulin . ^^^ Co localization for leptin , leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands . . ^^^
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We investigated associations between bone mineral density ( BMD ) and polymorphisms of the leptin receptor ( LEPR ) and estrogen receptor alpha ( ERalpha ) genes in young men . ^^^ DESIGN : BMD , anthropometric characteristics , and serum leptin concentrations were measured in young men and compared with regard to the LEPR and ERalpha genotype . ^^^ Estrogen receptor alpha gene polymorphisms Pvu 2 and Xba 1 influence association between leptin receptor gene polymorphism ( Gln223Arg ) and bone mineral density in young men . ^^^
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Adipose tissue gene expression in patients with a loss of function mutation in the leptin receptor . ^^^ Leptin receptor loss of function is a unique way to explore the role of leptin in the regulation of adipose tissue . ^^^ OBJECTIVE : We studied the consequences of the absence of leptin signaling on adipocyte gene expression in two girls with a mutation in the leptin receptor . ^^^ RESULTS : Ob mRNA levels in subjects lacking the leptin receptor were not overexpressed but were in the range that could be expected from their BMI ( 58 and 26 amol / micro g total mRNA , range in obese women : 26 69 ) . ^^^
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Recently , lower leptin binding to the soluble form of the leptin receptor ( LEPR ) was shown in carriers of the Arg 223 encoding allele of the Gln223Arg polymorphism of the LEPR . ^^^ These findings are consistent with a role of the Gln223Arg polymorphism in reducing peripheral and central leptin binding to the LEPR in humans . ^^^ The Gln223Arg polymorphism of the leptin receptor in Pima Indians : influence on energy expenditure , physical activity and lipid metabolism . ^^^
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The objectives were to : 1 ) clone a partial sequence ofthe equine leptin and leptin receptor genes so as to enable the design of primers for RT PCR determination of leptin and leptin receptor gene presence and distribution in tissues , 2 ) develop a radioimmunoassay to quantify peripheral concentrations of leptin in equine , 3 ) determine if peripheral concentrations of leptin correlate with body condition scores in equine , and 4 ) determine if changing body condition scores would influence peripheral concentrations of leptin in equine . ^^^ In Experiment 1 , equine leptin ( GenBank accession number AF 179275 ) and the long form of the equine leptin receptor ( GenBank accession number AF 139663 ) genes were partially sequenced . ^^^ Equine leptin receptor mRNA was detected in liver , lung , testis , ovary , choroid plexus , hypothalamus , and subcutaneous adipose tissues using RT PCR . ^^^
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Leptin receptor variant in women with polycystic ovary syndrome . ^^^
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We now show that leptin receptor labelling is expressed on somata , dendrites and axons , and is also concentrated at synapses in hippocampal cultures . ^^^
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The changes of serum leptin and soluble leptin receptor levels in patients undergoing mobilization of peripheral blood stem cells before autologous stem cells transplantation . ^^^ Serum leptin levels , soluble leptin receptor , cortisol , insulin , tumor necrosis factor alpha ( TNFalpha ) , and interleukin 1 receptor antagonist ( IL 1ra ) levels were measured in the withdrawn samples . ^^^ No significant changes were found in soluble leptin receptor , insulin , cortisol , and TNFalpha levels throughout three measurements , while IL 1ra levels increased significantly in the SC harvest phase compared to the previous two measurements . ^^^
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Soluble leptin receptor levels in patients with anorexia nervosa . ^^^ OBJECTIVE : To examine whether changes of serum soluble leptin receptor levels ( S LEPR ) can modify leptin half life and its tissue effects . ^^^
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Placental leptin receptor isoforms in normal and pathological pregnancies . ^^^ Alternate mRNA splicing of human leptin receptor generates four membrane isoforms with different C terminal sequences . ^^^
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In the past three years , scientists had cloned the obese gene , clarified the structure of leptin , nailed down and cloned the gene of leptin receptor , partly revealed the mechanisms of leptin ' s effects which make the study of obesity entering the molecular age . ^^^
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BACKGROUND : The adipocyte derived hormone leptin regulates food intake by stimulation of the long leptin receptor isoform in the hypothalamus . ^^^ The long leptin receptor is also expressed in the piriform cortex , an area involved in the relay of olfactory cues . ^^^
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We previously reported that deficiency of leptin receptor ( Ob R ( / ) , db / db ) in mice led to impaired NK cell function . ^^^ In the present paper , we , for the first time , found that human NK cell lines constitutively expressed leptin receptor ( Ob R ) , both long form Ob R ( Ob R ( L ) ) and short form Ob R ( Ob R ( S ) ) , using immunohistochemical method , Western blotting , and RT PCR assay . ^^^
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Because fibroblasts are essential for wound repair , we compared the in vitro behavior of fibroblasts cultured from diabetic , leptin receptor deficient ( db / db ) mice with wild type fibroblasts from mice of the same genetic background in processes important during tissue repair . ^^^ To address the question whether these differences resulted from chronic hyperglycemia or absence of the leptin receptor , fibroblasts were harvested from newborn db / db mice before the onset of diabetes ( 4 to 5 weeks old ) . ^^^ These fibroblasts showed no impairments in VEGF production under basal or hypoxic conditions , confirming that the results from db / db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin leptin receptor axis . ^^^ The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic , leptin receptor deficient db / db mice . ^^^
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Therefore , our objectives were to determine the effect of leptin on mammary epithelial cell proliferation , and the distribution of mRNA for two leptin receptor isoforms in prepubertal bovine mammary glands and other peripheral tissues . ^^^ In addition , we determined that MAC T cells and isolated bovine mammary epithelial cells express the long form of leptin receptor ( Ob Rb ) mRNA . ^^^ In contrast with reports on other species , mRNA expression of the short form of leptin receptor ( Ob Ra ) was detected only in bovine liver , pituitary body , and spleen . ^^^
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Plasma leptin and leptin receptor expression in childhood acute lymphoblastic leukemia . ^^^ To investigate whether leptin plays a role in acute lymphoblastic leukemia ( ALL ) , we investigated the levels of leptin in plasma with enzyme linked immunosorbent assays and the expression of the leptin receptor on malignant lymphoblasts with reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ To elucidate the underlying mechanism of this phenomenon , we analyzed the expression of the leptin receptor on the mononuclear cell populations of the patients . ^^^ Results of immunohistochemical staining supported these findings by showing that the tumor clones themselves do not express the leptin receptor . ^^^
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No significant effects were seen on circulating leptin levels or hypothalamic protein levels of the leptin receptor . ^^^
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In vitro interaction of the glycine receptor with the leptin receptor . ^^^ These in vitro studies identified the leptin receptor as a potential binding partner for GlyR , and this interaction was confirmed in binding studies that used the cytoplasmic loop of the GlyR as an affinity ligand for homogenized tissue from rat spinal cords and lower brainstem . ^^^ Mass spectrometric analyses of eluants showed that the leptin receptor was specifically extracted from the homogenized and solubilized tissue . ^^^ The long form of the leptin receptor is expressed in the hypothalamus ( as is the GlyR ) and among its other functions , it quickly evokes a satiation response upon binding leptin . ^^^ Our in vitro results suggest that this rapid initial response may be mediated through direct interaction of the leptin receptor with GlyR or a related nicotinicoid family member homolog . . ^^^
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Genes currently recognized to be involved include KAL 1 ( associated with 10 linked Kallmann Syndrome ) , gonadotropin releasing hormone ( GnRH ) receptor , gonadotropins , pituitary transcription factors ( HESX 1 , LHX 3 , and PROP 1 ) , orphan nuclear receptors ( DAX 1 , associated with 10 linked adrenal hypoplasia congenital , and SF 1 ) , and three genes also associated with obesity ( leptin , leptin receptor , and prohormone convertase 1 [ PC 1 ] ) . ^^^
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This paper reviews data on mammary leptin and leptin receptor gene expression as well as on blood and milk leptin levels during the pregnancy lactation cycle in humans , rodents and ruminants , with the aim of better understanding milk leptin origin and functions . ^^^
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The long form of the leptin receptor was shown to be expressed , and leptin induced the phosphorylation of STAT 3 in the three cell types . ^^^ The leptin receptor was also expressed by rodent and human intestinal L cells , and leptin ( 1 mg / kg i . p . ) significantly stimulated GLP 1 secretion in rats and ob / ob mice . ^^^
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Progress in the study of leptin receptor ] . ^^^
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Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure . ^^^ Body mass index adjusted serum levels of leptin and soluble leptin receptor were increased in patients with CHF compared to the controls ( 0 . 28+ / 0 . 03 vs . 0 . 22+ / 0 . 04 ng . m ( 2 ) / ml . kg and 32 . 6+ / 1 . 9 ng / ml vs . 22 . 9+ / 2 . 3 , P < 0 . 05 ) . ^^^
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Lack of the long form leptin receptor ( Ob Rb ) in db / db mice causes resistance . ^^^ We tested the effects of LPS in C57BL / 6J db ( 3J ) / db ( 3J ) ( BL / 3J ) mice , which express only the circulating leptin receptors , compared with C57BL / 6J db / db ( BL / 6J ) mice , which express all short form and circulating isoforms of the leptin receptor . ^^^
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Role of leptin and leptin receptor in inflammation . ^^^
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Five candidate genes including the lipoprotein lipase , leptin , leptin receptor , alpha adducin and beta 3 adrenergic receptor were selected to examine their possible contribution to essential hypertension ( EH ) in a Chinese population . ^^^
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METHODS : Leptin receptor expression and iNOS messenger RNA expression were evaluated by reverse transcriptase polymerase chain reaction . ^^^
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Extensive co expression of tyrosine hydroxylase ( a marker for dopamine neurons ) with both the insulin receptor and the leptin receptor was observed in the ventral tegmentum and substantia nigra . ^^^
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Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food deprived rats . ^^^ The effects of nicotine on the expressions of neuropeptide Y ( NPY ) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry . ^^^ The results show that NPY expression is not affected in the arcuate nucleus ( ARN ) and is increased only slightly in the paraventricular nucleus ( PVN ) by nicotine administration under normal ( i . e . fed ) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions . ^^^ Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus . ^^^ Nicotine administration resulted in decreased NPY and increased leptin receptor levels . . ^^^
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The leptin receptor is expressed in several hypothalamic nuclei including the arcuate nucleus . ^^^
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Growth hormone releasing factor decreases long form leptin receptor expression in porcine anterior pituitary cells . ^^^ Pituitary cells from six pigs , 180 200 days of age , were studied in primary culture to determine if growth hormone releasing factor ( GRF ) affects long form leptin receptor ( Ob Rl ) expression . ^^^
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In this study , the NPY gene promoter was transactivated by leptin in N18TG2 , NG 108 15 and PC 12 cells which expressed the functional leptin receptor . ^^^ The long isoform of leptin receptor ( OB Rb ) could induce the transactivation , but the C terminal truncated form ( OB Ra ) could not . ^^^
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To investigate the contribution of STAT 3 signalling to leptin action in vivo , we replaced the gene encoding the leptin receptor ( lepr ) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue ( lepr ( S 1138 ) ) that specifically disrupts the LRb STAT 3 signal . ^^^ Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form ( LRb ) . ^^^
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The heterozygous leptin receptor deficient ( Lepr ( db / + ) ) mouse develops spontaneous GDM and the fetuses display characteristics similar to infants of GDM mothers . ^^^
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Ontogenesis of leptin receptor in rat Leydig cells . ^^^ In this study , we evaluated the expression of leptin receptor ( Ob R ) in rat testes from gestational to adult age in comparison with the pattern of expression of relaxin like factor ( RLF ) , a specific marker of Leydig cell differentiation status . ^^^
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We have previously shown that ( 1 ) . leptin and leptin receptor ( Ob R ) are expressed in the human endometrium , and ( 2 ) . leptin secretion is regulated in blastocyst and endometrial epithelial cell ( EEC ) co cultures . ^^^ Interleukin 1beta ( IL 1beta ) up regulates leptin and Ob R , and both cytokines up regulate beta 3 integrin expression in EEC . ^^^ The blockade of Ob R neutralized the effects of both leptin and IL 1beta on expression of the IL 1beta system and beta 3 integrin and on phosphorylation of signal transducer and activator of transcription 3 ( Stat 3 ) . ^^^ These results suggest that leptin regulates the IL 1 system and that the blockade of functional Ob R impairs leptin and IL 1beta functions at the endometrial level . ^^^
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SHHF / Mcc fa ( cp ) rats ( SHHF ) were used to study the effect of gene dosage of a null mutation of the leptin receptor ( cp ) on salt sensitivity and response to a combined endothelin A and B receptor antagonist ( bosentan ) . ^^^
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The leptin receptor is known to signal through the janus kinase / signal transducer and activator of transcription ( JAK / STAT ) pathway to modulate transcription of target genes . ^^^
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The aim of the study was to characterize changes in serum ghrelin levels in obese subjects and their relationship to the serum levels of leptin and soluble leptin receptor . ^^^ The ghrelin serum levels ( 165 . 0+ / 58 . 1 vs . 343 . 37+ / 81 . 96 ; p < 0 . 001 ) and soluble leptin receptor serum levels ( 7 . 25+ / 3 . 44 vs . 21 . 80+ / 4 . 99 ; p < 0 . 0001 ) were significantly lower in obese patients . ^^^
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Serum leptin level was also significantly ( P < 0 . 05 ) lower in the DOS FO rats ; however , hypothalamic leptin receptor ( a and b ) mRNA and neuropeptide Y expressions were not altered by dietary fat sources . ^^^
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Developmental changes in plasma leptin and hypothalamic leptin receptor expression in the rat : peripubertal changes and the emergence of sex differences . ^^^ Leptin , the peptide hormone product of the ob gene , regulates food intake and energy expenditure at the hypothalamic level via the long form of the leptin receptor ( Ob Rb ) . ^^^
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Body composition , leptin , and the leptin receptor and their relationship to the growth hormone ( GH ) axis in growing wethers treated with zeranol . ^^^ Age related changes in body composition , leptin , and hypothalamic pituitary expression of the leptin receptor and associative relationships of these factors to constituents of the growth hormone ( GH ) axis were evaluated . ^^^ The leptin receptor in the pituitary appeared to be differentially ( P = 0 . 097 ) expressed across days 73 135 , but no differences ( P > or = 0 . 43 ) were detected in expression of this receptor in the hypothalamus among treatments and ages . ^^^ Serum leptin increased with age as did percent body fat , but zeranol did not influence body composition , serum leptin , or expression of the leptin receptor in the hypothalamus or pituitary ; however , the leptin receptor appeared to be differentially expressed among the hypothalamus and pituitary with level of body fat and leptin being inversely associated to transcriptional factors involved in somatotrope synthesis and secretion of GH . . ^^^
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It has been demonstrated that the SH 2 domain containing tyrosine phosphatase 2 ( SHP 2 ) negatively regulates STAT 3 mediated transcriptional activation through long form leptin receptor ( OBRb ) . ^^^
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Sexual dimorphism in cafeteria diet induced hypertension is associated with gender related difference in renal leptin receptor down regulation . ^^^ As leptin acts on the kidney to induce natriuresis , renal leptin receptor alterations could lead to a defect in sodium excretion and hence to hypertension . ^^^ Therefore , the present study investigated renal leptin receptor ( Ob Ra and Ob Rb ) mRNA and leptin binding capacities in diet induced hypertension . ^^^ Moreover , renal Ob R densities were inversely correlated to plasma leptin concentrations in male rats and testosterone treated female rats but not in female rats . ^^^
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OBJECTIVE : To investigate the association between leptin levels , polymorphisms in the leptin receptor ( LEPR ) gene , and weight gain . ^^^ Genetic variation in the leptin receptor gene , leptin , and weight gain in young Dutch adults . ^^^ Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation ( or a linked other marker ) may imply that these subjects have a modified functional leptin receptor . ^^^
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Among the animal models of early onset obesity , obese Zucker ( FA / FA ) rats ( which are homozygous for an inactivating missense mutation in the leptin receptor ) are particularly appropriate , because their linear growth shows this growth hormone independence . ^^^
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Soluble leptin receptor levels also increased significantly in serum , more or less in line with the leptin increase . ^^^ Our work represents the first report of visibly augmented leptin and soluble leptin receptor secretion in malarial infection . . ^^^
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No influence of surgical stress on postoperative leptin gene expression in different adipose tissues and soluble leptin receptor plasma levels . ^^^ Plasma soluble leptin receptor levels were measured in 23 children after cardiosurgery . ^^^ Plasma soluble leptin receptor levels decreased immediately after the onset of surgery and remained unchanged thereafter . ^^^ The measured increase in plasma leptin after surgery does not result from elevated levels of soluble leptin receptor but may follow an up regulation of leptin gene expression later after the operation due to postsurgical metabolic changes . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Phosphorylated JAK 2 was primarily bound to a short 106kDa leptin receptor isoform and to a lesser extent to a 210kDa molecule . ^^^
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Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation . ^^^ BACKGROUND : The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor ( SLEPR ) , and total , free and bound leptin , and the change in the serum SLEPR level during an IVF cycle . ^^^
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Leptin receptor defects in homozygous mutant Zucker fatty ( fa / fa ) rats lead to massive obesity , hyperphagia , decreased energy expenditure , and insulin resistance , while the phenotype of heterozygous ( Fa / fa ) lean rats lies between lean ( Fa / Fa ) and obese ( fa / fa ) rats . ^^^
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These effects of dexamethasone may not be due to the change in the expression level of the leptin receptor Ob Ra and Ob Rb isoforms . ^^^
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Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor , free leptin index , adiponectin , and resistin concentrations in healthy humans . ^^^ The adipocyte derived hormones leptin [ which circulates in a free form and bound to a soluble leptin receptor ( sOB R ) ] , adiponectin , and resistin play a key role in regulating energy homeostasis and metabolism . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To investigate whether leptin signaling limited to this brain area is sufficient to reduce food intake and body weight , we used adenoviral gene therapy to express the signaling isoform of the leptin receptor , lepr ( b ) , in the ARC of leptin receptor deficient Koletsky ( fa ( k ) / fa ( k ) ) rats . ^^^ Arcuate nucleus specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky ( fa ( k ) / fa ( k ) ) rats . ^^^ Restored leptin receptor expression in the ARC reduced both mean daily food intake ( by 13 % ) and body weight gain ( by 33 % ) and increased hypothalamic proopiomelanocortin mRNA by 65 % while decreasing neuropeptide Y mRNA levels by 30 % , relative to fa ( k ) / fa ( k ) rats injected with a control adenovirus ( Ad lacZ ) ( P < 0 . 05 for each comparison ) . ^^^ These findings collectively support the hypothesis that leptin receptor signaling in the ARC is sufficient to mediate major effects of leptin on long term energy homeostasis . ^^^
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These cells express the leptin receptor ObRb , and leptin can regulate POMC mRNA levels , but the cellular mechanisms by which this occurs is unknown . ^^^
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Disruption of the renal alpha 2 adrenoceptors or leptin receptor implicated in natriuresis control may also be an additive risk for the increase in tubular reabsorption in obesity hypertension . ^^^
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Serum leptin concentrations , hypothalamic leptin receptor mRNA and oestrogen induced leptin gene expression in fat increased with age and adiposity in pigs . ^^^
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Adipose leptin and hypothalamic Ob R mRNA were not different from controls , but resistin was increased ( P < . 05 ) , and muscle GLUT 4 content was decreased ( P < . 05 ) in ETOH offspring compared with controls . ^^^
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OBJECTIVE : To investigate the effects of leptin on platelet aggregation and platelet free calcium ( Ca ( 2+ ) ) concentrations , and the role of the long form of leptin receptor ( ObRb ) and the phospholipase C ( PLC ) in mediating leptin effects on platelet function . ^^^ MEASUREMENTS : ADP induced platelet aggregation and platelet Ca ( 2+ ) were measured after incubation of platelet rich plasma with leptin alone 5 200 ng / ml , leptin 200 ng / ml and anti human leptin receptor long form antibody ( ObRb Ab ) 5 10 microl , or leptin 200 ng / ml and PLC inhibitor U 73122 0 . 5 1 nmol / l . ^^^
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This study was carried out to analyze the process of liver regeneration in db / db mice which show severe steatosis because of abnormal leptin receptor . ^^^
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These were the leptin gene ( LEP ) , the leptin receptor gene ( LEPR ) , the catechol 0 methyltransferase gene ( COMT ) , the dopamine D ( 2 ) receptor gene ( DRD 2 ) , the estrogen 1 receptor gene ( ESR 1 ) , and the androgen receptor gene ( AR ) . ^^^
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Leptin receptor expression in the basolateral nucleus of amygdala of conditioned taste aversion rats . ^^^ AIM : To determine whether serum leptin level and the leptin receptor ( OB R ) expression in the basolateral amygdala ( BLA ) change following conditioned taste aversion ( CTA ) formation . ^^^ METHODS : The serum leptin concentration was measured by rat leptin RIA kit , long and short forms of leptin receptor ( OB Rb and OB Ra ) mRNA in the brain sections were examined by in situ hybridization ( ISH ) and the expression of OB R was assessed by immunohistochemistry ABC method with a highly specific goat anti OB R antibody . ^^^ Leptin and OB R maybe involved in neuronal communication for CTA . ^^^
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Our immunohistochemical observations indicate that the leptin receptor is distributed throughout the brain , including the hypothalamus , and interestingly , is found in the hippocampus and neocortex . ^^^
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New leptin receptor mutations in mice : Lepr ( db rtnd ) , Lepr ( db dmpg ) and Lepr ( db rlpy ) . ^^^ Three new spontaneous recessive mouse mutations in the leptin receptor gene ( Lepr ) , Lepr ( db rtnd ) , Lepr ( db dmpg ) and Lepr ( db rlpy ) , originated in the CBA / J ( CBA ) , B10 . ^^^
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Activation of the leptin receptor by a ligand induced conformational change of constitutive receptor dimers . ^^^ Binding of leptin to the leptin receptor is crucial for body weight and bone mass regulation in mammals . ^^^ Using a quantitative Bioluminescence Resonance Energy Transfer approach , we show here in living cells that approximately 60 % of the leptin receptor exists as constitutive dimers at physiological expression levels in the absence of leptin . ^^^ No further increase in leptin receptor dimerization was detected in the presence of leptin . ^^^ Importantly , in cells expressing the short leptin receptor isoform , leptin promoted a robust enhancement of energy transfer signals that reflect specific conformational changes of pre existing leptin receptor dimers and that may be used as read out in screening assays for leptin receptor ligands . ^^^
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The present study was aimed at detecting chicken leptin receptor ( cOb R ) expression in isolated chicken islets of Langerhans and to examine the direct effect of leptin on insulin secretion after stimulation by acetylcholine ( 1 micro M ) + glucose ( 14 mM ) from isolated perfused chicken pancreas . ^^^
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In contrast , leptin did not influence 11beta HSD 1 expression in primary hepatocytes from db / db mice , indicating that leptin regulation of 11beta HSD 1 expression is probably mediated by the functional leptin receptor . ^^^
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From day 3 through week 10 , DIO and DR rats had similar mRNA expression of arcuate nucleus neuropeptide Y , proopiomelanocortin , agouti related peptide , and all splice variants of the leptin receptor ( OB R ) . ^^^
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Using polymerase chain reaction ( RT PCR ) , a 346 and 375 base fragment indicative for the short and long leptin receptor isoform was detected in the rat heart . ^^^ We speculate that the effect might be mediated by both leptin receptor isoforms . ^^^
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Diurnal and ultradian dynamics of serum adiponectin in healthy men : comparison with leptin , circulating soluble leptin receptor , and cortisol patterns . ^^^
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Soluble leptin receptor levels in patients with chronic renal failure . ^^^ Soluble leptin receptor ( SLR ) is the extracellular part of the leptin receptor . ^^^ Serum soluble leptin receptor levels did not differ between these groups ( 19 . 1+ / 11 . 3 vs . 19 . 6+ / 6 . 1 U . ml ( 1 ) ) . ^^^ We conclude that soluble leptin receptor levels in patients with chronic renal failure do not differ from those of healthy subjects despite higher serum leptin levels in CRF patients . ^^^
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The Zucker Diabetic Fatty ( ZDF ) rat is a model of impaired insulin sensitivity arising from hyperphagia owing to a mutation in the leptin receptor . ^^^
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Soluble leptin receptor and soluble receptor bound fraction of leptin in the metabolic syndrome . ^^^ OBJECTIVE : In obesity , plasma leptin is high and soluble leptin receptor ( sOb R ) levels are low , resulting in a low fraction of bound leptin . ^^^
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Indeed , the placenta expresses mRNA for Ob Ra , one of the short forms of the leptin receptor ( Ob R ( S ) ) important in leptin transport , and this expression increases markedly in late pregnancy . ^^^ Therefore , we determined the transplacental passage of maternal leptin to the fetus in the rat and whether this transport increases near term in association with a rise in placental expression of Ob R ( S ) protein . ^^^
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However , the leptin receptor is expressed not only in the central nervous system , but also in peripheral tissues , such as haematopoietic and immune systems . ^^^ Moreover , the leptin receptor bears homology to members of the class 1 cytokine family , and recent data have demonstrated that leptin is able to modulate the immune response . ^^^ Thus , the leptin receptor is expressed in human peripheral blood mononuclear cells , mediating the leptin effect on proliferation and activation . ^^^ In vitro activation and HIV infection in vivo induce the expression of the long isoform of the leptin receptor in mononuclear cells . ^^^
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Association between leptin receptor gene polymorphisms and early onset prostate cancer . ^^^ OBJECTIVE : To report a case control study examining the relationship between polymorphisms in the leptin receptor ( OBR ) gene and the development of young onset prostate cancer , because epidemiological studies report that prostate cancer risk is associated with animal fat intake , and thus we investigated if this association occurs via this genetic mechanism . ^^^ CONCLUSION : This case control study showed no significant association between leptin receptor gene polymorphisms and the risk of young onset prostate cancer , suggesting that genetic variations in OBR are unlikely to have a major role in the development of early onset prostate cancer in the UK . . ^^^
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This study examined the levels of neuropeptide Y ( NPY ) , and of Y 1 , Y 2 , Y 5 and leptin receptor mRNA expression in the hypothalamic arcuate nucleus ( Arc ) of chronic high energy diet induced obese ( DIO ) and resistant ( DR ) mice . ^^^ In DIO mice , the levels of NPY and leptin receptor mRNA expressions were significantly higher than in LF mice ( +32 and +14 % , P < 0 . 001 and 0 . 05 respectively ) , indicating central leptin resistance , whereas the DR and LF groups did not differ . ^^^
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We demonstrate complex formation between clusterin and leptin by several approaches and show that the binary complex retains the ability to transduce the leptin signal via binding to the leptin receptor and activation of the Janus kinase / signal transducer and activator of transcription pathway . ^^^
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The ins and outs of leptin receptor activation . ^^^ The leptin receptor is a member of the class 1 cytokine receptor family , which uses the Janus kinase / signal transducer and activator of transcription pathway as a major signaling route . ^^^ In this review , we focus on the molecular mechanisms underlying leptin receptor activation . ^^^
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To evaluate how these two treatments affect hypothalamic peptide systems involved in energy homeostasis , we compared patterns of hypothalamic neuropeptide Y ( NPY ) , agouti related protein ( AgRP ) , proopiomelanocotin ( POMC ) , and leptin receptor gene expression in acutely food deprived and chronically food restricted rats . ^^^ Leptin receptor expression was not affected by either treatment . ^^^ Double in situ hybridization histochemistry revealed that , in contrast to the situation in the arcuate nucleus , NPY and leptin receptor mRNA expressing neurons were not colocalized in the DMH . ^^^
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Changes in circulating leptin , leptin receptor , and gonadal hormones from infancy until advanced age in humans . ^^^ We determined developmental changes in circulating levels of the soluble leptin receptor ( sOB R ) , leptin , and gonadal hormones in human subjects . ^^^
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Polar expression and phosphorylation of human leptin receptor isoforms in paired , syncytial , microvillous and basal membranes from human term placenta . ^^^ The aim of this study was to investigate leptin receptor isoform expression and phosphorylation in paired , syncytial , microvillous and basal membranes from human term placenta by Western blot analysis . ^^^ The hormone leptin ( OB ) and its receptor ( OB R ) are key homeostatic regulators of mammalian body weight . ^^^ To test the phosphorylation capacity of the OB R isoforms , microvillous and basal membrane vesicles loaded with ATP were stimulated with leptin and the phosphorylation status of the OB R at the tyrosine 985 ( Y 985 ) was determined . ^^^
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In patients with acromegaly , total leptin increases following successful pituitary surgery and during somatostatin ( SMS ) analogue therapy ( despite no change in BMI ) but whether this represents changes in soluble leptin receptor , bound or free leptin is unclear . ^^^ A single batch measurement of leptin , bound leptin ( BL ) , soluble leptin receptor ( SLR ) , insulin and glucose were performed on samples from baseline and first occurrence of serum IGF 1 normalization . ^^^
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These altered DIO leptin and ghrelin responses were associated with 10 % lower leptin receptor mRNA expression in the arcuate ( ARC ) , dorsomedial ( DMN ) , and ventromedial hypothalamic nuclei and 13 and 15 % lower ghrelin receptor ( GHS R ) mRNA expression in the ARC and DMN than in the DR rats . ^^^
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Angiogenesis related genes that showed aberrant expression level are matrix metalloproteinase 2 ( MMP 2 ) , plasminogen activator inhibitor ( PAI ) , integrin , transforming growth factor beta ( TGF beta ) , vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , and leptin receptor . ^^^ Expression levels for these genes , except for leptin receptor , showed less in chorionic villi from RPL patients than those from normal controls . ^^^
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This involved assessing [ 3H ] thymidine incorporation , alkaline phosphatase ( ALP ) activity , proteoglycan production , leptin receptor ( Ob R ) activity , and detection of Ob R using Western blot analysis . ^^^
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Pretreatment of these cells with anti leptin receptor ( Ob R ) antibody , protein kinase C ( PKC ) inhibitors , calphostin C , and GF109203X , or the antioxidant N acetylcysteine ( NAC ) blocked the effects of leptin . ^^^
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Expression of leptin and leptin receptor system in woman reproductive organs ] . ^^^ OBJECTIVE : To explore the expression of leptin , leptin receptor ( Ob R ) and related signaling proteins in woman reproductive organs . ^^^ The expression of mRNA of leptin and long isoform of leptin receptor ( Ob Rb ) was detected by in situ hybridization . ^^^ CONCLUSION : Leptin may have an effect on women ' s reproductive function through leptin receptor systems . . ^^^
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The long form leptin receptor ( ObRb ) is expressed at high levels in the hypothalamus , and regulates appetite and energy expenditure . ^^^
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Using RT PCR , we demonstrate that these cells express the short form ( OB Ra ) leptin receptor . ^^^
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The obese Zucker rat , an animal model of genetic obesity , exhibits differences in serotonin signaling as well as a mutated leptin receptor . ^^^
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A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells . ^^^ In this article we show that rabbit endometrial cells express leptin receptor and that human leptin triggers phosphorylation of signal transducer and activator of transcription 3 and up regulates the expression of interleukin 1 receptor type 1 as was previously found in human endometrial cells . ^^^ Analysis of a structural model of the leptin leptin receptor complex suggested that helices 1 and 3 of the human leptin structure were likely sites of interaction with the cytokine binding domain of leptin receptor . ^^^ Accordingly , we synthesized a peptide ( LPA 2 ) comprising helix 3 ( residues 70 95 ) and investigated its ability to inhibit leptin receptor function . ^^^ LPA 2 binds specifically and with high affinity ( Ki ~ 0 . 6 10 10 10 M ) to leptin receptor and is a potent inhibitor of its functions in rabbit endometrial cells . ^^^
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Leptin , soluble leptin receptor , and transforming growth factor beta 1 levels in minimal change nephrotic syndrome . ^^^ The soluble leptin receptor ( sOb R ) is a transport protein contributing to binding and activation of circulating leptin . ^^^
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Strikingly , leptin stimulates cell proliferation specifically in androgen independent DU 145 and PC 3 prostate cancer cells but not in androgen dependent LNCaP FGC cells , although both cell types express functional leptin receptor isoforms . c Jun NH 2 terminal kinase ( JNK ) has been shown recently to play a crucial role in obesity and insulin resistance . ^^^
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To investigate whether leptin is associated with breast cancer , we determined the expression of OB Rb in human breast epithelial HBL 100 cells and human breast carcinoma derived T 47D cells , determined whether leptin influenced the proliferation of these cells , and evaluated the structure of mammary tissue in genetically obese leptin deficient Lep ( ob ) Lep ( ob ) and leptin receptor deficient Lepr ( db ) Lepr ( db ) mice . ^^^
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Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans . ^^^ In contrast , immunostaining for the leptin receptor was found exclusively in the membranes of the glandular cells . ^^^ A high density of the leptin receptor was localised in the epithelia of the duct lumen . ^^^
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Lactation modulates diurnal expression profiles of specific leptin receptor isoforms in the rat hypothalamus . ^^^ We investigated the effects of lactation on diurnal changes in serum leptin and hypothalamic expression of the leptin receptor isoforms , Ob Ra , Rb , Rc , Re and Rf in rats . ^^^ Thus , selective changes in expression of specific isoforms of the leptin receptor may contribute to the hyperphagia of lactation in rats . . ^^^
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Short communication : Tissue distribution of leptin and leptin receptor mRNA in the bovine . ^^^ Detection of leptin and leptin receptor mRNA in various tissues is crucial to an understanding of leptin physiology in dairy cattle . ^^^ We report here evidence of leptin receptor gene expression in central and peripheral tissues of the bovine by reverse transcription and polymerase chain reaction analysis . ^^^ The mRNA for the long form of the leptin receptor , Ob Rb , was detectable in all four adipose depots , mammary parenchyma , semintendinosus muscle , liver , adrenal cortex , spleen , kidney , testis , mesenteric lymph node , lung , aorta , abomasum , duodenum , jejunum , ileum , hypothalamus , pituitary , brain stem , cerebral cortex , cerebellar cortex , pons , and pineal gland . ^^^ The mRNA for the short form of the leptin receptor , Ob Ra , was detectable in the liver , adrenal cortex , spleen , pituitary , and brain stem , but not in the other tissues surveyed . ^^^
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OBJECTIVE : To study the expression of leptin and long form of leptin receptors ( Ob R ( L ) ) messenger ribonucleic acid ( mRNA ) and protein in endometrium during mid luteal phase of patients with polycystic ovary syndrome ( PCOS ) . ^^^ METHODS : The expression of leptin and Ob R ( L ) mRNA in endometrium during mid luteal phase from 15 normal controls and 14 PCOS related anovulatory patients who underwent ovulation induction therapy were studied by in situ hybridization , and levels of leptin and Ob R ( L ) protein were investigated by immunohistochemical methods . ^^^ RESULTS : The expression of Ob R ( L ) mRNA and protein in endometrial glands of most patients with PCOS were weak or moderate positive , whereas the levels of Ob R ( L ) mRNA and protein were moderate or strong positive in those of the controls , there was significant difference between the two groups ; leptin mRNA and protein expression in endometrium of patients with PCOS and controls were not significantly different between the groups . ^^^
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Leptin induces angiogenesis by its proliferative effects on endothelial cells ( ECs ) via OB receptor ( OB Rb ) gene . ^^^
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The evaluation of leptin receptor reduction in adipocytes was based on real time PCR analysis of the mRNA levels , Western blot analysis of the proteins , and biochemical analysis of leptin signaling capability . ^^^
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Effects of acetate and butyrate on the expression of leptin and short form leptin receptor in bovine and rat anterior pituitary cells . ^^^ The effects of acetate and butyrate on leptin and leptin receptor ( OB R ) expression in bovine and rat anterior pituitary were examined . ^^^
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Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription 3 ( p STAT 3 ) remained elevated in association with a sustained elevation in DNA binding activity of STAT 3 in the hypothalamus throughout 16 d period of leptin infusion . ^^^ This study demonstrates a sustained elevation in hypothalamic leptin receptor signaling through Janus kinase STAT pathway despite an increased expression of SOCS 3 during chronic central leptin infusion . ^^^
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Leptin receptor activation downregulates many regulatory genes , including STAT 3 and PAP 1 . ^^^
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Recently published results revealed linkage of obesity traits to a chromosomal region near the leptin receptor gene ( Lepr ) locus in high body weight selected big and fat DU6i mice . ^^^ Therefore , we assume that the mutation in the C 2 domain of Lepr alone might not result in impaired leptin binding or signaling . . ^^^ A novel leptin receptor variant with a conservative amino acid substitution ( I 359 5 ) in body weight selected and unselected mouse lines . ^^^
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Leptin receptor deficient Zucker ( fa / fa ) rat retards the development of pig serum induced liver fibrosis with Kupffer cell dysfunction . ^^^ The aim of this study was to investigate the role of leptin in the development of liver fibrosis with Kupffer cell function using leptin receptor deficient rats . ^^^ These results suggest that leptin receptor deficiency retards the development of liver fibrosis due to the dysfunction of Kuppfer cells . . ^^^
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In addition , leptin receptor mRNA expression was 23 % lower in the arcuate nuclei of 4 to 5 wk old DIO compared with DR rats . ^^^
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Leptin and leptin receptor expression in the rat ovary . ^^^ In this study leptin mRNA expression in the immature gonadotropin primed rat ovary increased 3 fold after human chorionic gonadotropin administration , followed by a dramatic increase in mRNA for both the short form ( Ob Ra ) and the long form ( Ob Rb ) of the leptin receptor ( approximately 8 and 7 fold , respectively ) . ^^^ Using immunohistochemistry , we observed protein expression of the long form of the leptin receptor ( Ob Rb ) in the ovary , with high intensities observed in oocytes and endothelial cells as well as thecal cells and corpora lutea . ^^^
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Hypothalamic leptin receptor and signaling molecule expressions in cafeteria diet fed rats . ^^^
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OBJECTIVE : To investigate the relationship between leptin receptor ( Lepr ) gene Gln223Arg polymorphism and obstructive sleep apnea hypopnea syndrome ( OSAHS ) . ^^^
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Functional analysis of leptin receptor activation using a Janus kinase / signal transducer and activator of transcription complementation assay . ^^^ The leptin receptor ( LR ) , a member of the class 1 cytokine receptor family , is composed of a single subunit . ^^^
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Expression of leptin receptor ( Ob R ) isoforms and signal transducers and activators of transcription ( STATs ) mRNAs in the mouse taste buds . ^^^ In conclusion , the present study provides evidence of the existence of the leptin receptor , Ob Rb , and STAT 3 in the mouse taste bud cells . ^^^
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Amongst these genes , sequence variations in the adrenergic receptors , uncoupling proteins , peroxisome proliferator activated receptor , and the leptin receptor genes are of particular relevance . ^^^
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Partial cloning and localization of leptin and leptin receptor in the mammary gland of the Egyptian water buffalo . ^^^ Furthermore , several isoforms of leptin receptor were found both in the central nervous system and in the peripheral tissues . ^^^ Our results show that , short and long isoforms of leptin receptor are expressed in buffalo mammary gland tissue . ^^^
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Characterization of bone structure in leptin receptor deficient Zucker ( fa / fa ) rats . ^^^ To investigate the role of leptin in bone formation , the skeleton of the obese female leptin receptor deficient Zucker rat was examined using pQCT , microCT , and histomorphometry . ^^^ Leptin deficiency or leptin receptor deficiency results in higher bone mass . ^^^ In an attempt to further investigate leptin ' s role in bone formation , we examined the skeleton of obese leptin receptor deficient Zucker rats . ^^^ METHODS : Female leptin receptor deficient Zucker ( fa / fa ) rats and their homozygous ( Fa / Fa ) and heterozygous ( Fa / fa ) lean controls were used at 9 and 15 weeks of age ( n = 5 ) . ^^^
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Using immunofluorescence microscopy , we demonstrated a polarized expression pattern of leptin receptor protein on the surface of mononuclear cells and constitutive expression of GH in PBMCs . ^^^
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METHODS AND RESULTS : Femoral artery endoluminal wire injury was performed in diabetic insulin 2 Akita ( ins2Akita ) and leptin receptor db / db ( leprdb / db ) mutant mice . ^^^
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This effect on PEPCK mRNA was not due to an alteration in the relative abundance of the leptin receptor or the ability of PEPCK to respond to cAMP . ^^^
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Both DIO and DR animals were found to have reduced long form leptin receptor expression and enhanced basal P STAT 3 in the hypothalamus with respect to Chow . rAAV leptin caused an increase in STAT 3 phosphorylation and proopiomelanocortin expression in the hypothalamus and an increase in uncoupling protein 1 in brown adipose tissue in both Chow and DR animals , but failed to do so in DIO . ^^^
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The importance of leptin in regulating sexual maturation is supported by data showing that deletions of the leptin gene or alterations in the leptin receptor result in infertility . ^^^
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We recently found that a functional leptin receptor is present on polymorphonuclear neutrophils ( PMNs ) and may be able to influence their oxidative capacities . ^^^
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Interestingly , we documented the absence of leptin receptor expression in human diabetic foot ulcers . ^^^
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Therefore , we examined distribution of leptin receptor containing neurons transsynaptically connected with the porcine fat tissue by means of combined viral transneuronal tracing and immunohistochemical staining method . ^^^ Pseudorabies virus ( PRV ) was injected into the perirenal fat tissue in pigs , and after survival periods of 3 , 5 , 7 , 9 , and 11 days , hypothalami were processed immunohistochemically with primary antisera against PRV and leptin receptor ( OBR ) . ^^^
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Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor Ob Rb . ^^^
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To clarify the mechanism of leptin resistance during pregnancy , we measured plasma leptin concentrations , free to total leptin ratio ( percent free leptin ) and soluble leptin receptor concentrations in pregnant women , and compared the results with those in non pregnant women . ^^^ On the other hand , soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women ( r = 0 . 470 , P < 0 . 01 and r = 0 . 493 , P < 0 . 01 , respectively ) but not in non pregnant women . ^^^ These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women . . ^^^
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Increased leptin receptor transgene dose effects on obesity / diabetes and fertility / lactation in lepr db / db mice . ^^^ We have generated mice that are homozygous for a leptin receptor transgene that is expressed exclusively in neurons ( NSE LEPR B ) . ^^^ Transgenic complementation of leptin receptor deficiency . 2 . ^^^ We had previously shown that this transgene in the hemizygous state is effective in ameliorating almost all aspects of leptin receptor deficiency . ^^^
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Leptin and insulin downregulate leptin receptor gene expression in chicken derived leghorn male hepatoma cells . ^^^ In addition , we developed a specific chicken leptin receptor real time reverse transcription ( RT ) PCR , and downregulation of leptin receptor gene expression by homologous and heterologous signals was demonstrated , as relative leptin receptor mRNA levels were significantly decreased after exposure of LMH cells to recombinant chicken leptin or porcine insulin . ^^^ Finally , the ability of insulin and leptin to regulate chicken leptin receptor gene expression suggests a direct role of leptin in the control of hepatic metabolism . . ^^^
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Increased soluble leptin receptor in children with nephrotic syndrome . ^^^ The goal of this study was to elucidate the role of the soluble leptin receptor ( sOB R ) in maintaining serum leptin levels in nephrotic patients . ^^^
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OBJECTIVES : To elucidate the role of leptin on maxillo facial morphological growth using hereditary obesity model ob / ob mice , and to examine the presence of the leptin receptor gene expression in the mouse condylar head cartilage . ^^^ Furthermore , the condylar head cartilage in C57BL / 6J mice was stereoscopically excised to extract total RNA , and RT PCR method was performed regarding the leptin receptor gene . ^^^ Furthermore , the expression of the leptin receptor gene in the condylar head cartilage was confirmed . ^^^
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The Zucker fa / fa rat is a genetic model of obesity related to a default in the leptin receptor . ^^^
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High insulin or glucose levels in the brain could result in leptin resistance as manifested by food intake , which is probably due to the attenuation of STAT 3 phosphorylation downstream the leptin receptor . . ^^^
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Here , we sought to extend our previous studies by evaluating ( 1 ) the ontogeny of leptin receptor mRNA levels in rat brain and pituitary and ( 2 ) pituitary leptin protein levels in neonatal and pre pubertal rats . ^^^ Significant age related effects on leptin receptor mRNA levels were also observed in the pituitary and the hypothalamus of male and female rats using semi quantitative RT PCR analysis . ^^^ Immunohistochemical detection of leptin receptor immunoreactivity ( all forms ) revealed the presence of OBR like protein in pituitary and hypothalamus as early as PD 4 . ^^^ Cortical leptin receptor mRNA levels were similar throughout early postnatal development . ^^^ No gender related differences in leptin receptor mRNA levels were noted in brain or pituitary . ^^^
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Leptin receptor polymorphism is associated with serum lipid levels and impairment of cholesterol lowering effect by simvastatin in Japanese men . ^^^ OBJECTIVE : To investigate whether leptin receptor ( Ob R ) Arg223Gln polymorphism influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG CoA reductase inhibitor , simvastatin [ Clin . ^^^
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After leptin , there was increased expression of tyrosine 1141 phosphorylated leptin receptor , which may contribute to STAT 3 activation . ^^^ This process appears to be mediated by the JAK / STAT pathway via the leptin receptor long form and the H2O2 dependent p 38 and ERK1 / 2 pathways via activated JAK . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of leptin receptor isoforms in vitro : lack of effects of leptin on endometrial cytokine and MMP production . ^^^ METHOD OF STUDY : Reverse transcriptase polymerase chain reaction and immunocytochemistry were used to determine the pattern of expression of leptin receptor isoforms in primary human endometrial epithelial and stromal cells in culture . ^^^ CONCLUSIONS : This study shows for the first time , the presence of leptin receptor isoforms on endometrial , epithelial and stromal cells in culture . ^^^
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PML RARalpha is associated with leptin receptor induction : the role of mesenchymal stem cell derived adipocytes in APL cell survival . ^^^ We here report that primary acute promyelocytic leukemia ( APL ) cells express high levels of the leptin receptor ( OB R ) long isoform . ^^^
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Thus , leptin receptor is expressed in human peripheral blood mononuclear cells , mediating the leptin stimulation of proliferation and activation , the production of proinflammatory cytokines from cultured monocytes , and the prevention of apoptotic death in serum deprived monocytes . ^^^
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The soluble leptin receptor is crucial for leptin action : evidence from clinical and experimental data . ^^^ OBJECTIVE : The soluble leptin receptor ( sOB R ) was recently identified as the main leptin binding protein in human blood . ^^^ For our in vitro cell model , mouse pre B cells , transfected with the long form of the murine leptin receptor ( BAF3 / L46 ) , were incubated with recombinant human leptin at two different basal levels ( 0 . 5 and 0 . 1 nM ) and with the sOB R at varying levels . ^^^ In the case of a massive excess of sOB R , is it likely to be inhibitory to leptin interaction with the tissue membrane bound OB R . . ^^^
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Leptin and leptin receptor in human seminal plasma and in human spermatozoa . ^^^ Furthermore , a soluble leptin receptor ( 145 kDa ) was found in human seminal plasma in the same specimen . ^^^ We also detected a 145 kDa leptin receptor isoform in ejaculated spermatozoa as a possible target of leptin action in the male genital tract , which was localized at the tail of spermatozoa by immunofluorescence microscopy only . ^^^ Spermatozoa with deteriorated membranes contained 49 . 2 + / 6 . 9 % leptin receptor signal intensity compared with spermatozoa having intact membranes ( p < 0 . 01 ) . ^^^
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The role of leptin receptor signaling in feeding and neuroendocrine function . ^^^
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Leptin is bound in blood by a high affinity binding protein identical with the soluble leptin receptor ( sOB R ) . ^^^
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Inhibiting leptin receptor signaling pathways within GnRH neurons abolished the latter effect , indicating a direct action on these cells . ^^^
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We present the first evidence that suppressor of cytokine signaling 3 ( SOCS 3 ) , a protein inhibiting Janus kinase / signal transducer and activator of transcription ( STAT ) signaling distal of the leptin receptor , conveys seasonal changes in leptin sensitivity in the Siberian hamster . ^^^
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Functional expression of the short isoform of the murine leptin receptor Ob Rc ( muB1 . 219 ) in Xenopus laevis oocytes . ^^^ Six leptin receptor isoforms have been identified and localized in different tissues . ^^^ Based on these works , we decided to investigate whether the murine short leptin receptor isoform Ob Rc ( muB1 . 219 ) could transport leptin when expressed in Xenopus laevis oocytes . ^^^ Coexpression of the human Na+ / glucose cotransporter and the leptin receptor showed that leptin increased sugar uptake into the oocytes . ^^^ These results demonstrate that the short leptin receptor Ob Rc is able to mediate binding and internalization of the hormone when expressed in oocytes and that it may perform intracellular signaling . . ^^^
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Furthermore , defects in the ob gene and the leptin receptor lead to the development of obesity in rodents . ^^^
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A cDNA encoding the long form of the turkey ( Meleagris gallopavo ) leptin receptor ( LEPR ) was cloned and sequenced . ^^^ The LEPR gene ( long form ) encodes a protein of 1147 amino acids that has features similar to other LEPRs including : a signal peptide , a single transmembrane domain , and specific conserved motifs defining putative leptin binding and signal transduction regions of the protein . ^^^ Molecular cloning and expression of the turkey leptin receptor gene . ^^^
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The mechanism ( s ) responsible for the development of skeletal muscle leptin resistance is unknown ; however , a role for increased suppressor of cytokine signaling 3 ( SOCS 3 ) inhibition of the leptin receptor has been demonstrated in other rodent tissues . ^^^
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The recombinant feline leptin with a molecular weight of 16 kDa induced phosphorylation of the signal transducers and activators of transcription 3 ( STAT 3 ) protein in the cells expressing rat leptin receptor . ^^^
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To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils , we monitored the effects of high dietary intake of n 3 PUFA on hepatic and muscular beta oxidation , plasma leptin concentration , leptin receptor gene expression , and in vivo insulin action . ^^^ The increased FA oxidation after n 3 PUFA supplementation of the high fat diet was accompanied by lower plasma leptin concentration ( 38 % , P < 0 . 05 ) and leptin mRNA expression ( 66 % , P < 0 . 05 ) in retroperitoneal adipose tissue , and elevated hepatic mRNA level for the leptin receptor Ob Ra ( 140 % , P < 0 . 05 ) . ^^^
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Real time PCR quantification of hypothalamic cDNA revealed a 100 % up regulation of neuropeptide Y and a 50 % suppression of GnRH expression accompanied by a 95 % attenuation of leptin receptor type B expression in obese female DBA / 2J mice . ^^^
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Double immunohistochemical staining confirmed that deletion of STAT 3 occurred in leptin receptor ( OB Rb isoform ) positive neurons . ^^^
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Moreover , the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions . ^^^
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Role of fat amount and type in ameliorating diet induced obesity : insights at the level of hypothalamic arcuate nucleus leptin receptor , neuropeptide Y and pro opiomelanocortin mRNA expression . ^^^ Using quantitative in situ hybridization , we found that the DIO mice had higher levels of leptin receptor ( LR , +290 % , p < 0 . 005 ) and neuropeptide Y ( NPY , +25 % , p < 0 . 05 ) mRNA expression in the hypothalamic arcuate nucleus ( Arc ) than the DR mice , whereas the level of pro opiomelanocortin ( POMC ) mRNA expression was significantly reduced ( 45 % , p < 0 . 01 ) . ^^^
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Furthermore , we measured the levels of leptin in the serum and hepatic leptin and leptin receptor messenger RNA ( mRNA ) expression in liver biopsy specimens of patients with NASH ( n = 5 ) and simple steatosis ( n = 5 ) . ^^^ Additionally , the serum leptin levels and the hepatic leptin receptor mRNA expression were not statistically different between patients with NASH and those with simple steatosis . ^^^
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Based on the presence in the rat adrenals of at least two Ob R isoforms and the conflicting findings on the effect of leptin on adrenocortical secretion , we investigated the effects of the native leptin and several leptin fragments ( 10 ( 8 ) and 10 ( 6 ) M ) on aldosterone and corticosterone secretion from freshly dispersed rat zona glomerulosa ( ZG ) and zona fasciculata reticularis ( ZF / R ) cells . ^^^ Taken together , our findings indicate that in rat adrenocortical cells leptin and leptin fragments may differently interact with Ob Rs or interact with different Ob R isoforms . ^^^
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Thus , this site of dense leptin receptor expression would be sensitive to physiological changes in leptin plasma concentrations . ^^^
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The lesions forming in response to injury strongly expressed leptin receptor mRNA and protein . ^^^ Exogenous leptin also enhanced lesion growth and increased cellular proliferation in injured arteries from wild type mice but had no effect on vessels from leptin receptor deficient db / db mice . ^^^ CONCLUSIONS : Our results raise the possibility that there might be a direct , leptin receptor mediated link between the hyperleptinemia in human obesity and the increased risk for cardiovascular complications associated with this condition . . ^^^
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A defective nutritional regulation of leptin receptor gene expression and reduced STAT 3 signaling may be involved in the development of leptin resistance in DIO . ^^^
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C57BL / KsJ db / db mice have obese and diabetic phenotypes because of disruption of the leptin receptor . ^^^ In addition , immunostaining of the leptin receptor and insulin like growth factor 1 receptor showed up regulation of these protein levels specifically in the lesions . ^^^
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The presence of leptin receptor in human PMN was determined both at mRNA and protein levels , and the effect of leptin on PMN activation , as assessed by CD11b expression , was evaluated using flow cytometry . ^^^ In contrast to monocytes , which express both the short and long forms of the leptin receptor ( Ob Ra and Ob Rb , respectively ) , PMN expressed only Ob Ra . ^^^
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Leptin receptor deficient MMTV TGF alpha / Lepr ( db ) Lepr ( db ) female mice do not develop oncogene induced mammary tumors . ^^^ We evaluated oncogene induced mammary tumor development in obese MMTV TGF alpha / Lepr ( db ) Lepr ( db ) mice that exhibit a defect in OB Rb , which is considered to be the major signaling isoform of the leptin receptor . ^^^ Serum leptin levels of MMTV TGF alpha / Lepr ( db ) Lepr ( db ) mice were 12 20 fold higher than levels of lean mice . ^^^ Thus , despite elevated serum leptin levels , leptin receptor deficient MMTV TGF alpha / Lepr ( db ) Lepr ( db ) mice do not develop mammary tumors . ^^^
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These include the thrombin receptor , the serotonin handling system , and the leptin receptor . . ^^^
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Leptin receptor isoform 219 . 1 : an example of protein evolution by LINE 1 mediated human specific retrotransposition of a coding SVA element . ^^^ One example is the SVA sequence , which forms the C terminal coding exon of the human leptin receptor isoform 219 . 1 . ^^^
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In sus scrofa , candidate genes associated with obesity and growth include Leptin Receptor , Melanocortin 4 Receptor , Agouti related protein , Heart fatty acid binding protein 3 , and Insulin like growth factor 2 . ^^^
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Expression of leptin receptor in laying hens was determined by RT PCR . ^^^ The highest expression of leptin receptor was observed in the hypothalamus . ^^^ Within the ovary , a relatively high expression of leptin receptor was found in the stroma with cortical follicles < 1 mm , the wall of white ( 1 8 mm ) and small yellow follicles ( > 8 12 mm ) , and the granulosa layer of F 3 follicles . ^^^ The expression of leptin receptor in the granulosa layer of F 2 and F 1 follicles was barely detectable . ^^^ This was in contrast to a much higher expression of leptin receptor maintained in the theca layer of F 3 F1 follicles . ^^^
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Leptin was first described to act on the satiety center in the hypothalamus through specific receptors ( leptin receptor [ ObR ] ) to restrict food intake and enhance energy expenditure . ^^^
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Leptin receptor signaling and the regulation of mammalian physiology . ^^^ While the hormone leptin and its receptor were discovered relatively recently , a great deal is already known about the molecular details of leptin receptor ( LR ) signaling and physiologic regulation . ^^^ Thus , other as yet undefined leptin receptor signals are central to these and perhaps other aspects of leptin action . . ^^^
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Novel players in negative regulation of central leptin receptor signaling have been identified and open the possibility that these may be important in the development of leptin resistance and obesity . ^^^ Recent progress in understanding central and peripheral leptin receptor signaling provides potential new targets for anti obesity and anti diabetes drug development . . ^^^
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The SHRSP fatty ( fa / fa ) rats have a missense mutation of the leptin receptor gene and plasma leptin concentrations are augmented . ^^^
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Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis . ^^^ The current study was designed to further clarify the role of leptin in liver disease by characterizing leptin and leptin receptor expression in the development and onset of experimental liver fibrosis . ^^^ Leptin and leptin receptor mRNA expression was determined by semiquantitative RT PCR , protein expression by Western blot analysis and localization of leptin and its receptor by immunohistochemistry . ^^^ Normal liver tissue does not express leptin , but leptin receptor mRNA . ^^^ Leptin receptor mRNA expression was not significantly altered in damaged livers . ^^^
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Consistent with this , the STAT 3 binding site on the leptin receptor is also required for this regulation . ^^^
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The lack of effect of leptin on resistin in db / db mice indicated that the leptin inhibitory action on resistin expression requires the long leptin receptor isoform . ^^^
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Serum pattern of circulating free leptin , bound leptin , and soluble leptin receptor in the physiological menstrual cycle . ^^^ OBJECTIVE : To investigate the serum pattern of free leptin , bound leptin , and soluble leptin receptor throughout the physiological menstrual cycle . ^^^ MAIN OUTCOME MEASURE ( S ) : Free leptin , bound leptin , soluble leptin receptor , LH , E ( 2 ) , P , vaginal ultrasound . ^^^ There were no significant alterations in serum bound leptin and soluble leptin receptor levels . ^^^ Circulating bound leptin and soluble leptin receptor are not altered by the cyclic hormone status . ^^^
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The changes in insulin parameters brought about by long term overfeeding were influenced most consistently by leptin receptor ( LEPR ) Gln223Arg and insulin like growth factor 2 Apa 1 polymorphisms . ^^^
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Genetic variations in the leptin receptor ( LEPR ) gene have been conceived to affect body weight in general populations . ^^^
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Aberrant expression and possible involvement of the leptin receptor in bladder cancer . ^^^ We also applied transient transfection followed by BrdU labeling and immunofluorescent staining to address the effect of the leptin receptor on bladder cancer cell growth . ^^^ RESULTS : Although leptin was not detected in the bladder tissue specimens , a decreased expression of the leptin receptor was observed in most cancer tissue specimens we analyzed . ^^^ Furthermore , the forced expression of the leptin receptor in T 24 bladder cancer cells prevented them from entering the S phase . ^^^ CONCLUSIONS : Our data demonstrated for the first time that the leptin receptor is aberrantly expressed in bladder cancer tissue and is possibly involved in the carcinogenesis of bladder cancer . . ^^^
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Aberrant expression and possible involvement of the leptin receptor in endometrial cancer . ^^^ In this study , we analyzed the expression and possible involvement of leptin and the leptin receptor in the pathogenesis of endometrial cancer . ^^^ METHODS : Radioimmunoassay was performed to analyze the serum leptin levels in the endometrial cancer patients , while RT PCR , immunoblotting , and immunohistochemistry techniques were applied to study the expression of leptin receptor in the endometrioid type endometrial cancer tissues . ^^^ Furthermore , BrdU labeling followed by immunofluorescent analysis was used to analyze the effect of leptin receptor overexpression on endometrial cancer cell proliferation . ^^^ On the other hand , lower expression levels of leptin receptor short form ( Ob Ra ) were observed in most endometrial cancer tissues , especially in the poorly differentiated ones , and the forced expression of Ob Ra in RL 95 2 endometrial cancer cells prevented them from entering the S phase . ^^^
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Hexokinase 1 , GLUT 3 , and lactate dehydrogenase A and B were ubiquitous , whereas GLUT 2 , monocarboxylate transporters 1 and 2 , and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity . ^^^
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GCs rapidly inhibited the leptin induced STAT 3 phosphorylation in a dose and time dependent manner , as assayed by Western blotting using anti phosphospecific STAT 3 in human hepatoma cell lines ( Huh 7 ) transiently expressing long form leptin receptor . ^^^
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Initially thought to be adipocyte specific , the ob gene , as well as the leptin receptor , has been found in a variety of other tissues . ^^^
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The leptin receptor ( LEPR ) gene consists of 20 exons divided over 1 . 75 Mb . ^^^ A missense mutation in the bovine leptin receptor gene is associated with leptin concentrations during late pregnancy . ^^^
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The fa leptin receptor mutation and the heritability of respiratory frequency in a Brown Norway and Zucker intercross . ^^^ We sought to determine whether the fa ( leptin receptor ) mutation was a major determinant of the putative obesity effects on respiratory frequency in an intercross between the Brown Norway ( low breathing frequency , nonobese strain ) and the Zucker ( moderately high breathing frequency , with the fa mutation ) strains . ^^^ Breathing parameters during the hypoxic , hypercapnic , and combined challenges demonstrated a wide range of heritability from 5 to 96 % , with a very nonuniform proportion of heritability explained by the leptin receptor . ^^^ At best , for frequency 4 . 5 min into the hypercapnic hypoxic challenge , approximately 20 % of the total heritability ( approximately 67 % ) could be attributed to an effect of the leptin receptor mutation . ^^^
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Leptin and soluble leptin receptor in follicular fluid . ^^^ The relationship between intrafollicular leptin and the soluble leptin receptor , ovarian hormones , and oocyte quality was examined to determine potential factors contributing to this finding . ^^^ METHODS : Follicular fluid leptin , soluble leptin receptor , hormones , and oocyte quality were examined in 84 individual follicles from 30 women undergoing in vitro fertilization . ^^^ RESULTS : Follicular fluid leptin and soluble leptin receptor levels correlated inversely with each other ( r = 0 . 354 ; p = 0 . 001 ) . ^^^ Follicular fluid leptin levels correlated with intrafollicular estradiol ( r = 0 . 42 ; p < 0 . 001 ) , progesterone ( r = 0 . 48 ; p < 0 . 001 ) , and androstenedione ( r = 0 . 49 ; p < 0 . 001 ) , whereas soluble leptin receptor levels correlated with activin ( r = 0 . 38 ; p < 0 . 001 ) and follistatin ( r = 0 . 35 ; p < 0 . 002 ) . ^^^
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Leptin receptor gene transfer into the arcuate nucleus of female Fatty zucker rats using recombinant adeno associated viral vectors stimulates the hypothalamo pituitary gonadal axis . ^^^ Fatty fa / fa Zucker rats with a missense mutation in the leptin receptor ( OB R ) are obese and infertile with prolonged estrous cycles . ^^^ Recombinant adeno associated viral ( rAAV ) vectors encoding the human leptin receptor gene ( rAAV OB Rb ) were microinjected intraparenchymally to produce doxycycline regulatable OB R gene expression . ^^^
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Modulation of direct leptin signaling by soluble leptin receptor . ^^^ Soluble leptin receptor ( SLR ) represents the major leptin binding activity in plasma . ^^^
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Not only the classical JAK 2 ( Janus kinase 2 ) STAT 3 ( signal transducer and activator of transcription 3 ) pathway , but also the phosphatidylinositol 3 kinase phosphodiesterase 3B cAMP pathway mediates hypothalamic leptin receptor signaling . ^^^ It appears that hypothalamic leptin resistance , possibly due to defective nutritional regulation of leptin receptor expression and / or reduced STAT 3 signaling in the hypothalamus , contributes to the development of obesity associated with high fat feeding and aging . ^^^
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The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65 % energy restriction . ^^^ No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed . ^^^ Leptin responsiveness to energy restriction : genetic variation in the leptin receptor gene . ^^^ It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor . ^^^
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BiaCore analysis of leptin leptin receptor interaction : evidence for 1 : 1 stoichiometry . ^^^ Analyzing the binding mode and the reaction stoichiometry allowed us to conclude that the leptin receptor dimerization is not induced by ligand binding . ^^^ Similar results were observed for the affinity of different species of leptin binding to mouse leptin receptor . . ^^^
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Identification and expression cloning of a leptin receptor , OB R . ^^^ A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin AP fusion protein to identify a leptin receptor ( OB R ) . ^^^
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Leptin receptor expression in fetal lung increases in late gestation in the baboon : a model for human pregnancy . ^^^ Therefore , we employed the baboon ( Papio sp . ) , a well characterized primate model for human pregnancy , to determine the presence and ontogeny of leptin receptor in fetal lung with advancing gestation . ^^^ Lungs were collected from fetal baboons , early in gestation ( days 58 62 , n = 4 ) , at mid gestation ( days 98 102 , n = 4 ) , and late in gestation ( days 158 165 , n = 4 ) ( term 184 days ) . mRNA transcripts for leptin ( LEP ) and both long and short intracellular domain isoforms of the leptin receptor ( LEP R ( L ) and LEP R ( S ) ) were assessed by RT PCR . leptin receptor protein was evaluated by immunoblotting and cell types expressing leptin receptor were identified in late pregnancy by immunohistochemistry . ^^^ However , transcripts for both LEP R ( L ) and LEP R ( S ) receptor isoforms increased several fold ( P < 0 . 05 ) in fetal lung between mid and late gestation , while leptin receptor protein was detectable only in late pregnancy . leptin receptor was localized in distal pulmonary epithelial cells , including type 2 pneumocytes . ^^^ Collectively , these and past findings may suggest a modulatory role for the polypeptide in pulmonary development and / or may identify leptin receptor as a physiological marker of primate fetal lung maturity . . ^^^
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This study examines the hypothesis that in ovariectomized ( OVX ) rats modification of estrogen levels or treatment with a selective estrogen receptor modulator , raloxifene ( RAL ) , alters leptinemia and modulates leptin receptor ( Ob R ) abundance in hypothalamus and white adipose tissue , similar to the modification of adipose status induced by hypoestrogenism . ^^^
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High leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice . ^^^ In this study we demonstrate that histamine deficiency elevates serum leptin level and decreases full length leptin receptor isoform with a slight increase of the short one and results in mild late onset obesity . ^^^ Leptin acts through its receptor ( OBR ) , the product of db gene that activates the Jak / STAT pathway predominantly . ^^^
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Neuropeptidergic characterization of the leptin receptor mutated obese Koletsky rat . ^^^ An additional model , the obese ( f / f ) Koletsky rat with a nonsense leptin receptor mutation has not been fully characterized . ^^^
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The purpose of this study was to characterize leptin receptor isoform mRNA expression in leptin treated DU 145 and PC 3 prostate cancer cell lines . ^^^ No defect in SOCS 3 signaling was observed , and proliferation appears to be working through the PI3K and MAPK leptin receptor activated pathways , depending on cell type . ^^^
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Long term exercise down regulates leptin receptor mRNA in the arcuate nucleus . ^^^ The purpose of this study was to investigate the effects of exercise on blood leptin concentrations and expression of leptin receptor subtype b ( Ob Rb ) mRNA in the arcuate nucleus of hypothalamus ( ARC ) . ^^^
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In the arcuate nucleus , dorsomedial nucleus of the hypothalamus , and ventral premammillary nucleus , CART neurons also express leptin receptor long form splice variant . ^^^
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Resistance arises from impaired leptin transport across the blood brain barrier ( BBB ) , defects in leptin receptor signaling , and blockades in downstream neuronal circuitries . ^^^
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Expression and localisation of leptin and leptin receptor in the mammary gland of the dry and lactating non pregnant cow . ^^^ Leptin and leptin receptor were studied in the mammary gland of non pregnant dry and lactating cows . ^^^
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The purpose of our study was to investigate associations of serum adiponectin with BMD ( DXA and QCT ) , FM ( DXA and QCT ) , and serum leptin and soluble leptin receptor levels in 38 women and 42 men ( age 39 81 , BMI 17 55 , 86 % with type 2 diabetes ) . ^^^
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Expression of 1300 transcripts was evaluated by microarray with total mRNA extracted from mid layer aortic smooth muscle of 3 week old SHR / Izumo and WKY / Izumo rats . mRNAs encoding sodium dependent neurotransmitter transporter , epidermal growth factor precursor , EEF 2 , leptin receptor long isoform b , clathrin assembly protein short form , and preprocomplement 3 ( pre pro C 3 ) were expressed only in aortic smooth muscle from SHR by microarray and by reverse transcription polymerase chain reaction analysis . ^^^
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Low levels of expression of leptin receptor at the cell surface result from constitutive endocytosis and intracellular retention in the biosynthetic pathway . ^^^ The leptin receptor is mainly localized in intracellular compartments in target tissues . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Here , we investigate the expression pattern of total leptin receptor ( OB R ( T ) ) , the long form ( OB R ( L ) ) and short isoforms HuB219 . 1 and HuB219 . 3 in the human endometrium . ^^^ Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part . ^^^ Leptin receptor was localized at the epithelial and glandular epithelium using in situ hybridization . ^^^
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Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet induced obesity : role of leptin in the regulation of hypothalamic long form leptin receptor expression . ^^^ The objectives of this study were to determine if reduced long form leptin receptor ( ObRb ) expression in diet induced obese ( DIO ) animals is associated with deficits in maximal leptin signaling and , secondly , to establish the effects of short term caloric restriction ( CR ) on ObRb expression and function . ^^^
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OBJECTIVE : To investigate the association between bone mineral density ( BMD ) and leptin receptor ( LEPR ) polymorphism ( Gln 223 Arg ) in young women and postmenopausl osteoporotic women . ^^^ Bone mineral density and leptin receptor polymorphism Gln223Arg in Han women in Beijing ] . ^^^ Correlation was found between BMD and leptin receptor polymorphism ( Gln 223 Arg ) at lumbar spine ( r = 0 . 151 , P < 0 . 05 ) . ^^^ CONCLUSION : Leptin receptor polymorphism ( Gln 223 Arg ) has association with peak bone mass in young women , which may be used as genetic marker in predicting the risk of developing osteoporosis in Chinese women of Han nationality . . ^^^
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We investigated the effect of inhibition of 11beta HSD with glycyrrhetinic acid ( GE ) , an effective 11beta HSD inhibitor , on body weight regulation in obese Zucker rats , which have a defect in the leptin receptor gene . ^^^
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OBJECTIVE : Although the role of the leptin receptor ( LEPR ) in obesity is well recognized , its role in insulin sensitivity remains unknown . ^^^ Association of leptin receptor polymorphism with insulin resistance . ^^^
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We generated kinase positive and kinase negative erbB 2 tagged with YFP and the long form of leptin receptor ( LEPRb ) tagged with CFP . ^^^ Both short and long isoforms of leptin receptor phosphorylated and thereby activated erbB 2 upon leptin binding and enhanced MAPK activity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Evidence has been provided that leptin affects corticosteroid hormone and insulin secretion , and therefore we have investigated in the rat the expression of leptin receptor expression in adrenal cortex and pancreatic islets , as well as the effects of the acute treatment with leptin and leptin fragments 150 167 , 138 167 , 93 105 , 22 56 and 26 39 on the plasma concentrations of aldosterone , corticosterone , insulin and glucagon . ^^^
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We also found that FGF 19 acutely increased liver expression of the leptin receptor ( 1 . 8 fold ; P < 0 . 05 ) and decreased the expression of acetyl coenzyme A carboxylase 2 ( 0 . 6 fold ; P < 0 . 05 ) . ^^^
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Effects of leptin receptor gene 3 ' untranslated region polymorphism on metabolic profiles in young Japanese men . ^^^ We investigated the effects of leptin receptor gene 3 ' untranslated region ( 3 ' UTR ) polymorphism on clinical and metabolic parameters in 221 young Japanese men aged 21 to 28 years . ^^^ The polymerase chain reaction restriction fragment length polymorphism method was used to identify a pentanucleotide ( CTTTA ) insertion in 3 ' UTR of the leptin receptor gene . ^^^ These findings suggest that serum HDL cholesterol and apoA 1 levels are influenced by the leptin receptor gene 3 ' UTR polymorphism in young Japanese men . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
These eight genes are apolipoprotein E ( APOE ) , type 1 collagen alpha 1 ( COL1A1 ) , estrogen receptor alpha ( ER alpha ) , leptin receptor ( LEPR ) , parathyroid hormone ( PTH ) / PTH related peptide receptor type 1 ( PTHR 1 ) , transforming growth factor beta 1 ( TGF beta 1 ) , uncoupling protein 3 ( UCP 3 ) , and vitamin D ( 1 , 25 dihydroxyvitamin D 3 ) receptor ( VDR ) . ^^^
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Physiologic estradiol levels enhance hypothalamic expression of the long form of the leptin receptor in intact rats . ^^^
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In a subsequent study , body weight and plasma concentrations of leptin were measured weekly in layer and broiler chicks from day 1 to 35 of age and brain leptin receptor and neuropeptide Y ( NPY ) mRNA expression were analyzed at 1 , 9 , and 35 days of age . ^^^ Leptin receptor and NPY mRNA were expressed in brain from day 1 in chicks of both genotypes and increased significantly to day 35 of age . ^^^ Furthermore , acquisition of the anorectic effect of leptin is likely to be associated with greater expression of the leptin receptor and NPY mRNAs than to changes in blood levels of leptin . ^^^
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Obesity related genetic factors including common polymorphisms in the leptin gene ( LEP A19G and G 2548A ) and its receptor ( LEPR Q223R ) were investigated in DNA available for 376 patients and 805 controls . ^^^ Body mass index , leptin and leptin receptor polymorphisms , and non hodgkin lymphoma . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We tested the hypothesis that common exonic variants in the leptin ( LEP ) and leptin receptor ( LEPR ) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites ( n = 397 ) and blacks ( n = 143 ) . ^^^ Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals : the HERITAGE family study . ^^^
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We show that SH SY5Y cells express leptin , the long and short isoforms of the leptin receptor ( ObRl , ObRs ) . ^^^
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RECENT FINDINGS : As delineated in murine models , STAT 3 independent signals triggered by the leptin receptor are clearly important in fertility , and candidate pathways such as those via phosphatidylinositol 3 kinase and extracellular signal related kinase are implicated in leptin regulated cascades . ^^^
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In addition , leptin receptor gene expression in the hypothalamic arcuate nucleus ( ARC ) and ventromedial nucleus of HE rats was reduced . ^^^
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We therefore examined in the fetal sheep hypothalamus during late gestation gene expression for leptin receptor ( OB Rb ) and neuropeptides that regulate energy balance in the adult . ^^^
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Furthermore , the association of the polymorphisms and PTP1B and leptin receptor ( LepR ) gene gene interactions with complications of type 2 diabetes were examined in type 2 diabetic patients . ^^^ A synergistic effect of PTP1B and LepR variants on the leptin signalling may be involved . . ^^^ Tyrosine phosphatase 1B and leptin receptor genes and their interaction in type 2 diabetes . ^^^
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OBJECTIVE : To assess the relationship of the variation of exon 20 of leptin receptor ( LEPR ) gene to the lipid metabolism and fat distribution of the children with obesity . ^^^ Relationship of variation 3057 G > A of exon 20 of leptin receptor gene to lipid metabolism and fat distribution of children with obesity ] . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor expression on T lymphocytes modulates chronic intestinal inflammation in mice . ^^^ Wild type ( WT ) or leptin receptor deficient ( db / db ) RB ( high ) cells were transferred into scid mice and development of colitis evaluated . ^^^
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Correlation analysis between single nucleotide polymorphism of the leptin receptor intron 8 and fatness traits in chickens ] . ^^^ Leptin receptor plays an important role in leptin functioning signal transduction and it may have direct effects on the deposition of adipose tissues and the body weight , the leptin receptor ( OBR ) gene , therefore , can be considered as a candidate gene in the study of fat deposition of the chicken . ^^^
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Leptin receptor deficient rats and mice also show impaired LTP in CA 1 and poor performance in the water maze . ^^^
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Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis . ^^^
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The leptin / leptin receptor system shows strong similarities to the long chain cytokine interleukin 6 ( IL 6 ) and granulocyte colony stimulating factor cytokine / receptor systems . ^^^ The effect of the mutations on leptin receptor ( LR ) signaling and on binding to the membrane proximal cytokine receptor homology domain ( CRH 2 ) of the LR was determined . ^^^
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In a second series of experiments , peripheral blood mononuclear cells ( PBMC ) were isolated from venous blood to determine the effect of stimulation with the polyclonal mitogen , concanavalin A ( ConA ) , on the long form of the leptin receptor ( Ob Rl ) mRNA abundance , and to determine whether leptin altered mitogen induced proliferation , cytokine production , or signal transducer and activator of transcription 3 ( STAT 3 ) activation . ^^^
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This study determines the effect of DM on liver I / R using a murine model of type 2 DM in which the leptin receptor is defective . ^^^
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Finally , control rats under the dietary deprivation period presented higher levels of uncoupling protein 2 mRNA and lower levels of leptin receptor mRNA compared with the reference control group . ^^^
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We have previously identified suppressor of cytokine signaling 3 ( Socs 3 ) as a leptin induced negative regulator of leptin receptor signaling and potential mediator of leptin resistance . ^^^ We report here that Socs 3 ( + / ) mice display greater leptin sensitivity than wild type control mice : Socs 3 ( + / ) mice show both enhanced weight loss and increased hypothalamic leptin receptor signaling in response to exogenous leptin administration . ^^^
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This strain was created by classical breeding methods used to introgress the defective leptin receptor gene ( Lepr ( fa ) ) from insulin resistant Zucker fatty rats into the inbred BBDR / Wor strain background . ^^^
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Enhanced expression of leptin and leptin receptor ( OB R ) in human breast cancer . ^^^ PURPOSE : To evaluate leptin and leptin receptor ( OB R ) expression in human breast cancer and determine whether it could be effective for the prevention and treatment of breast cancer . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In leptin receptor deficient obese Zucker rats , with 75 % higher body weight than lean littermates , GALP mRNA levels in the ARC were decreased by 75 % , while neuropeptide Y ( NPY ) mRNA levels were increased 7 fold ( n = 5 , p < 0 . 001 ) , consistent with earlier reports . ^^^ The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions , and possible abnormalities in GALP neuronal signalling and their putative targets , thyrotropin releasing hormone and gonadotropin hormone releasing hormone neurons , under pathophysiological conditions such as diabetes and obesity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Two isoforms of the leptin receptor are enhanced in pregnancy specific tissues and soluble leptin receptor is enhanced in maternal serum with advancing gestation in the baboon . ^^^ Although it has been linked to receptor mediated pathways that directly influence human conceptus development , mechanisms that regulate the leptin receptor in pregnancy specific tissues remain unclear . ^^^ Therefore , we assessed leptin receptor ontogeny and regulation in the baboon ( Papio sp . ) , a primate model for human pregnancy . ^^^ Maternal serum was sampled with advancing gestation , and the abundance of soluble leptin receptor ( solLepR ) , a potential mediator of gestational hyperleptinemia , was determined . ^^^ Two placental leptin receptor isoforms ( 130 and 150 kDa ) increased ( P < 0 . 04 and P < 0 . 02 , respectively ) in abundance with advancing gestation . ^^^
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Leptin significantly inhibited energy intake of both LF fed and HF fed mice , and this was associated with a significant increase in hypothalamic long form leptin receptors with no change in short form leptin receptor or brown fat uncoupling protein 1 mRNA expression . ^^^
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Leptin , the 16 kDa peptide hormone product of the ob gene , is produced primarily by adipocytes and was initially thought to exert its effects exclusively through actions on the hypothalamus via distinct leptin receptors termed OB R . ^^^ Ischemia and reperfusion significantly downregulated leptin and OB R expression , although this was more pronounced in male rat hearts . ^^^
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The leptin receptor ( Ob R ) has six isoforms and can signal through either the MAPK or the Janus activated kinase / signal transducer and activator of transcription signal transduction pathway , depending on the isoform . ^^^ Expression of Ob R has been reported in human and mouse oocytes ; however , the physiological role of leptin during follicular development and oocyte maturation is largely unknown . ^^^
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Expression of leptin receptor isoforms and effects of leptin on the proliferation and hormonal secretion in human pituitary adenomas . ^^^ OBJECTIVE : To pursue whether leptin regulates anterior pituitary cells , we studied the ex vivo expression of several isoforms of the leptin receptor ( OB R ) as well as the in vitro effects of leptin administration in human pituitary adenomas . ^^^ METHODS : OB R mRNA expression and in vitro response to leptin were studied in 39 pituitary macroadenomas . ^^^ CONCLUSIONS : ( 1 ) Several isoforms of the OB R , including the signal transducing full length receptor , are expressed in most human pituitary adenomas . ( 2 ) This expression ex vivo is not associated with significant effects of leptin in vitro . . ^^^
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Deficiencies of leptin or leptin receptor , adiponectin and IL 6 are associated with obesity , insulin resistance and a propensity to type 2 diabetes . ^^^
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METHODS : Expressions of Ob gene product , leptin and its receptor , Ob R were investigated in 36 cases of HCC specimens and corresponding adjacent non tumorous liver tissues with immunohistochemical staining . ^^^
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Conversely , hypothalamic IL 1beta mRNA levels were reduced by 30 % in fa / fa ( Zucker ) rats , a model of genetic obesity caused by leptin receptor mutation ( P = 0 . 01 vs . lean littermates ) , and the effect of ADX to increase hypothalamic IL 1beta mRNA levels in fa / fa rats ( P = 0 . 02 ) is similar to that seen in normal animals . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The expression of leptin receptor and , in some species , leptin , in the placenta suggests a role for leptin in placental development , but this role has not been elucidated . ^^^
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The postnatal decline in BW due to leptin was associated with a decline in food intake ( P = 0 . 01 ) and hypothalamic leptin receptor ( P = 0 . 008 ) and neuropeptide Y ( P = 0 . 008 ) immunoreactivities and an increase in alpha melanocyte stimulating hormone ( P = 0 . 008 ) immunoreactivity . ^^^
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Using the chemical inhibitor of Janus kinase 2 ( Jak 2 ) activity , AG 490 , and overexpression of the suppressor of cytokine signaling 3 ( SOCS 3 ) , we show that blockade of leptin receptor ( Ob Rb ) phosphorylation blocks leptin induced HSC proliferation . ^^^
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In adjacent sections , a few cells immunoreactive to both ACTH and leptin receptor were detected . ^^^ A few cells were immunoreactive to both insulin and leptin receptor . ^^^ Moreover , in prosencephalon , mesencephalon , rhomboencephalon and spinal cord , ACTH immunoreactive cells were detected in the same areas as the leptin receptor immunoreactive cells . ^^^
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Relation between Leptin receptor gene polymorphisms , renal substantial hypertension and kidney damage in hypertension ] . ^^^
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Western blot analysis revealed that a biologically active leptin receptor isoform is expressed in mouse retinal endothelial cells . ^^^ Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells , where it upregulated vascular endothelial growth factor ( VEGF ) mRNA expression . ^^^
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In this work , we demonstrate that leptin inhibits the l alpha lysophosphatidic acid ( LPA ) induced intracellular calcium mobilization in a dose dependent manner in HEK 293 cells stably expressing full length leptin receptor ( OB Rb ) . ^^^
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Because radiation at a young age may affect the hypothalamus causing leptin receptor insensitivity , we hypothesized that a polymorphism in the leptin receptor ( LEPR ) gene , Gln223Arg , might influence susceptibility to obesity in survivors of childhood ALL . ^^^ Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia : a report from the Childhood Cancer Survivor Study . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Gene expression ( by in situ hybridisation ) in the hypothalamic arcuate nucleus for leptin receptor ( OB Rb ) , neuropeptide Y ( NPY ) , pro opiomelanocortin ( POMC ) and agouti related peptide ( AGRP ) was unaffected by photoperiod treatment , but food restriction increased NPY and AGRP mRNAs , in experiment 1 . ^^^
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RT PCR for leptin receptor expression revealed that FRTL 5 cells possess the gene transcript to the long cytoplasmic form of the receptor . ^^^
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Effect of dieting on plasma leptin , soluble leptin receptor , adiponectin and resistin levels in healthy volunteers . ^^^ MEASUREMENTS : Plasma concentrations of leptin , soluble leptin receptor protein ( sOB R ) , adiponectin , resistin , thyroid hormones and beta hydroxybutyrate were determined following overnight fast before and after the 4 week reduced calorie diet . ^^^
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In studies on patients and animal model , Tiangui Recipe was found to decrease peripheral androgen and insulin levels and lead to central regulation of proopiomelanocortin , neuropeptide Y and leptin receptor , as well as regulation of neuro endocrine metabolic network . ^^^
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In 16 pre eclamptic placentas , the expressions of leptin , hypoxia inducible factor 1alpha ( HIF1alpha ) and leptin receptor mRNAs were analyzed by semi quantitative reverse transcriptase polymerase chain reaction and compared with clinical data . ^^^ The co expressions of leptin and the isoforms of the leptin receptor were observed in all the pre eclamptic placentas . ^^^ The level of the expression of leptin mRNA was correlated with the placental HIF1alpha mRNA level and fetal body weight , but not with the levels of the leptin receptor isoforms in the pre eclamptic placentas . ^^^
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For this purpose , we evaluated in control and hypothalamic damaged rats : ( a ) in vivo and in vitro adrenocortical function , ( b ) adrenal leptin receptor immunodistribution and mRNA expression , and ( c ) whether the inhibitory effect of leptin on adrenal function remains . ^^^ Our results indicate that , compared to normal counterparts , pseudoobese animals displayed ( 1 ) hyperadiposity , despite being hypophagic and of lower body weight , ( 2 ) in vivo and in vitro enhanced adrenocortical response to ACTH stimulation , ( 3 ) an in vitro adrenal fasciculata reticularis cell hyper sensitivity to ACTH stimulus , ( 4 ) hyperplasia of their adrenal zona fasciculata cells , and ( 5 ) adrenal fasciculata reticularis cell refractoriness to the inhibitory effect of leptin on ACTH stimulated glucocorticoid production due , at least in part , to decreased adrenal leptin receptor expression . ^^^
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Both leptin and leptin receptor are essential for apolipoprotein M expression in vivo . ^^^ It was found that in both liver and kidney , expression of apoM was significantly lower in leptin deficient ob / ob mice and in leptin receptor deficient db / db mice than in control mice . ^^^ We conclude that both leptin and leptin receptor are essential for the apoM expression , indicating that leptin is physiologically regulating apoM synthesis in vivo . . ^^^
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Reverse transcription polymerase chain reaction ( RT PCR ) demonstrated that human GCs expressed mRNA of leptin and mRNA of isoforms of leptin receptor , including one long form and two types of short forms . ^^^
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The expression of leptin receptor in tissue culture of lactating mammary gland was augmented approximately 25 times by prolactin , but had no effect on virgin calf mammary tissue . ^^^ No effect of prolactin on leptin and leptin receptor expression was found in mammary gland tissue culture from calves . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
This study investigated the expression profile of placental leptin and leptin receptor isoforms in preeclampsia , using placental tissue from normal pregnancies that were matched in gestational age and birth weight as controls . ^^^ There was no significant difference in immunostaining for leptin receptor between both severe and mild preeclampsia compared with controls ( p > 0 . 05 ) . ^^^ However , there was no difference in the expression of all leptin receptor isoforms in placental tissue between preeclamptic and normal pregnancies . ^^^
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A new function of the leptin receptor : mediation of the recovery from lipopolysaccharide induced hypothermia . ^^^ Obese ( f / f ) Koletsky rats lack the leptin receptor ( LR ) , whereas their lean ( F / ? ) counterparts bear a fully functional LR . ^^^
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Lepr ( db / db ) mice are obese due to a defect in the signaling portion of the leptin receptor , which has led to extensive study of this highly conserved system over the past several years . ^^^ An allelic series for the leptin receptor gene generated by CRE and FLP recombinase . ^^^ Lepr ( db / db ) mice are obese due to a defect in the signaling portion of the leptin receptor , which has led to extensive study of this highly conserved system over the past several years . ^^^
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Leptin is a JAK 2 activating cytokine via the long form leptin receptor ( Ob Rb ) . ^^^
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Leptin receptor expression increases in placenta , but not hypothalamus , during gestation in Mus musculus and Myotis lucifugus . ^^^ Because similar placenta specific changes in leptin receptor expression occurred in species from distantly related mammalian taxa which collectively comprise approximately 70 % of all known mammalian species , it is possible that placental actions of leptin are conserved across mammals , even in those species ( such as the Swiss Webster strain of mouse ) in which the placenta does not itself produce leptin . . ^^^ In this study , the hypothesis that the placenta is also a target organ for leptin in diverse taxa was tested by examining the expression of leptin receptors ( Ob R ) in placentae from species of distantly related mammalian taxa , Mus musculus ( the laboratory mouse ) and Myotis lucifugus ( the little brown myotis , also called the little brown bat ) . ^^^ The increase in Ob R mRNA expression in placenta was specific , since Ob R mRNA expression did not change during gestation in either species in hypothalamus , the major site of the central actions of leptin . ^^^ Thus , Ob R is expressed in placenta throughout gestation in mice and bats , and its expression increases over the course of gestation , which raises the possibility that leptin may exert temporally distinct effects on placental growth or function throughout gestation . ^^^
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The long form of the leptin receptor resembles cytokine receptors , which include the interleukin 6 receptor . ^^^
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Contrarily to what happens in wild type mice , leptin increased galactose uptake in db / db animals ; since these mice lack the functional long leptin receptor , the measured effect may be due to the short receptor signaling . ^^^
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Expression of apoM is significantly decreased in leptin deficient ( ob / ob ) mouse or leptin receptor deficient ( db / db ) mouse . ^^^
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Endometrial leptin and leptin receptor expression in women with severe / moderate endometriosis . ^^^ In the present study , we compare the expression of leptin receptor mRNA during the pre receptive ( LH+2 ) and receptive ( LH+9 ) phases in the eutopic endometrium from patients with severe / moderate endometriosis ( n = 30 ) versus fertile controls ( n = 12 ) . ^^^ However , no difference was found in the expression pattern of the total leptin receptor OB RT , or in its long OB RL and soluble HuB219 . 3 forms when the eutopic endometria of patients with severe / moderate endometriosis and fertile controls were compared . ^^^ By means of in situ hybridization , total leptin receptor mRNA was localized in the luminal epithelium and the glands of the endometrium . ^^^ The immunohistochemical analysis of the long form of leptin receptor was also performed in order to confirm these findings at the protein level . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor in the chicken ovary : potential involvement in ovarian dysfunction of ad libitum fed broiler breeder hens . ^^^ To determine whether leptin is involved in the nutritional and reproductive interactions controlling follicular hierarchy in hens , blood leptin levels and ovarian expression of the leptin receptor mRNA were determined during follicle maturation in three chicken lines ; a slow growing broiler `` Label ' ' genotype without reproductive dysfunction , a fast growing `` Standard ' ' genotype fed ad libitum or restricted and a fast growing `` Experimental ' ' line with intermediate reproductive performance levels . ^^^ Whereas expression of the leptin receptor mRNA did not change in the theca , it clearly decreased with follicular differentiation in the granulosa of slow growing hens . ^^^ In fast growing standard hens fed ad libitum and presenting significant reproductive dysfunction , the decrease was disrupted and dramatic up regulation of granulosa cell expression of the leptin receptor was observed . ^^^ On the other hand , feed restriction decreased the overall level of expression of the leptin receptor mRNA and restored the decrease with follicular growth . ^^^
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Malnutrition during lactation in rats is associated with higher expression of leptin receptor in the pituitary of adult offspring . ^^^ OBJECTIVE : Recent studies have shown that leptin receptor is expressed in human and rat pituitary glands . ^^^ The expression of leptin receptor in rats whose dams were malnourished during lactation has not been previously reported . ^^^ METHODS : We examined leptin receptor expression in the pituitary gland of adult rats whose dams were assigned to one of the following groups during lactation : control diet , protein restricted diet ( 8 % protein ) , or energy restricted diet ( the control diet fed in restricted quantities that were calculated according to the mean ingestion of the protein restricted group ) . ^^^ After weaning , all pups had free access to the control diet until they reached adult age , at which time leptin receptor expression in the pituitary was analyzed by immunohistochemistry . ^^^
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The expression of leptin receptor and the activation of signaling pathways were studied by Western immunoblotting . ^^^ RESULTS : MCF 7 cells were found to express the leptin receptor and respond to leptin with cell growth and activation the signal transducers and activators of transcription 3 , extracellular signal regulated kinase 1 / 2 , and Akt / GSK3 / pRb pathways . ^^^
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Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus . ^^^ OBJECTIVE : We investigated whether or not serum levels of the soluble leptin receptor ( sOB R ) and leptin are related to anthropometric and metabolic changes during pubertal development of children and adolescents with type 1 diabetes mellitus . ^^^ RESULTS : OB R serum levels and parallel values of the molar ratio between sOB R and leptin were significantly higher in children with diabetes than in normal children ( P < 0 . 05 ) in almost all investigated Tanner stages . ^^^
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PML RARalpha expressing acute promyelocytic leukemia ( APL ) cells express high levels of leptin receptor ( OB R ) . ^^^ Adipocytes derived from mesenchymal stem cells ( MSC ) protect APL cells from drug induced apoptosis partially through the interaction of the membrane bound form of leptin and OB R . ^^^
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Effects of leptin and dexamethasone on long and short leptin receptor mRNA . ^^^ METHODS : The authors studied leptin receptor regulation by leptin and dexamethasone in the human hepatocellular carcinoma cell ( HepG 2 ) . ^^^ Expression of OB R219 . 1 and OB R219 . 3 , two short isoforms of leptin receptor , were also reduced in cells treated with leptin most remarkably at 10 ( 7 ) M for OB R219 . 1 ( 44 % of the control ) and at 10 ( 6 ) M for Ob R219 . 3 ( 49 % of the control ) . ^^^
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METHODS : Using immunohistochemical staining on archival paraffin embedded tissue sections , we studied the expression of leptin and leptin receptor in hydatidiform moles , with gestational age matched normal first trimester placenta used as control . ^^^ Reverse transcriptase polymerase chain reaction ( RT PCR ) was further performed using RNA extracted from frozen tissue ( five CHMs , four PHMs and nine normal first trimester placenta ) to study the expression of leptin and individual leptin receptor isoforms at the transcription level . ^^^ Significantly higher immunostaining intensity was shown for both leptin ( P < 0 . 05 ) and leptin receptor ( P < 0 . 001 ) in both CHMs and PHMs compared to normal first trimester placenta . ^^^ RT PCR revealed that the expression of leptin and all leptin receptor isoforms were significantly higher in both CHMs and PHMs than in normal placenta ( P < 0 . 05 ) . ^^^ CONCLUSIONS : There is up regulated expression of leptin and leptin receptor in GTDs . ^^^
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Taken together , these findings allows us to conclude that native leptin and its fragments interact differently with Ob Rs or interact with different Ob R isoforms , thereby variously modulating secretion and growth of cultured rat adrenocortical cells . . ^^^
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Collectively , these results suggest that a primary function of Shp 2 in postmitotic forebrain neurons is to control energy balance and metabolism , and that this phosphatase is a critical signaling component of leptin receptor ObRb in the hypothalamus . ^^^
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Initially thought to be adipocyte specific , the ob gene , as well as the leptin receptor , has been found in a variety of other tissues including the stomach . ^^^
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The expression of leptin receptor ( Ob R ) in rabbit ovary at day 9 of pseudopregnancy was evaluated by immunohistochemistry and Western blot analysis . ^^^ Ob receptor in rabbit ovary and leptin in vitro regulation of corpora lutea . ^^^
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Hormonal regulation of leptin and leptin receptor expression in porcine subcutaneous adipose tissue . ^^^ Leptin receptor mRNA abundance was decreased by 25 % with the combination of insulin and dexamethasone , relative to insulin treated adipose tissue slices ( P < 0 . 05 ; n = 4 ) . ^^^ Porcine GH decreased leptin receptor mRNA abundance by 17 % ( P < 0 . 05 ; n = 6 ) . ^^^
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These leptin induced effects are eliminated by inhibitors of leptin receptor ( OB R ) signaling . ^^^ Herein the impact of blocking leptin / OB R signaling in the mouse endometrium was assessed . ^^^ Intrauterine injection of either leptin peptide antagonists ( LPA 1 or 2 ) or OB R antibody on d 3 of pregnancy impaired mouse implantation in comparison to intrauterine injection of scrambled peptides ( LPA Sc ) or species matched IgGs . ^^^
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Leptin , soluble leptin receptor and leptin gene polymorphism in relation to preeclampsia risk . ^^^ Few investigators have simultaneously evaluated leptin , soluble leptin receptor ( SLR ) and leptin gene polymorphisms in preeclampsia cases and controls . ^^^
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We addressed the role of leptin in alcohol related behaviors by studying ethanol consumption in two strains of spontaneously mutant mice that lack leptin ( ob / ob ) or the leptin receptor ( db / db ) . ^^^
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Soluble leptin receptor and leptin levels in pregnant women before and after delivery . ^^^ Soluble leptin receptor is an extracellular domain of the leptin receptor that serves as the main leptin binding protein and may play a role in the regulation of leptin tissue effects . ^^^ The aim of our study was to assess serum concentrations of leptin , soluble leptin receptor , and other hormones involved in the regulation of leptin secretion in pregnant women before and after delivery . ^^^ In contrast , no differences between these groups were found in soluble leptin receptor levels . ^^^ Delivery significantly decreased serum leptin and cortisol levels and increased soluble leptin receptor levels ( 12 . 3+ / 9 . 1 ng / mL , 749 . 6+ / 205 . 3 nmol / L , 23 . 3+ / 7 . 9 U / mL , respectively ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Secretion of leptin from adipose tissue communicates body energy status to the neuroendocrine system by activating the long form of the leptin receptor ( LRb ) . ^^^
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Single nucleotide polymorphisms in the leptin receptor gene : studies in anorexia nervosa . ^^^ The leptin receptor has been mapped to a similar region , further upstream of this susceptibility locus . ^^^ Single nucleotide polymorphisms ( SNPs ) in the leptin receptor are associated with measures of body weight . ^^^ In the present study , SNPs in the coding region of the leptin receptor were analysed and their possible association with anorexia nervosa was investigated . ^^^ Two cohorts of young women , 176 Caucasian anorexia nervosa patients and 152 normal Caucasian females , were genotyped for three SNPs in the leptin receptor . ^^^
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We assess here ( 1 ) whether AMPK activity is diminished in rodents deficient in leptin or the leptin receptor , and ( 2 ) the effects of treating the diabetes prone , leptin receptor deficient Zucker Diabetic Fatty ( ZDF ) rat with an AMPK activator . ^^^ RESULTS : AMPK activity was diminished in muscle and / or liver of fa / fa ( leptin receptor deficient , non diabetic ) and ZDF ( leptin receptor deficient , diabetes prone ) rats and ob / ob mice ( leptin deficient ) . ^^^ CONCLUSIONS / INTERPRETATION : The results indicate that a deficiency of leptin or the leptin receptor is associated with a decrease in AMPK activity in muscle and / or liver . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Melanocortin 4 receptor gene ( MC4R ) variants are associated with obesity and binge eating disorder ( BED ) , whereas the more prevalent proopiomelanocortin ( POMC ) and leptin receptor gene ( LEPR ) mutations are rarely associated with obesity or BED . ^^^ The complete coding regions of MC4R , POMC , and leptin binding domain of LEPR were comparatively sequenced in 300 patients ( 233 women and 67 men ; mean + / SEM age , 42 + / 1 years ; mean + / SEM body mass index , 43 . 5 + / 0 . 3 kg / m2 ) undergoing laparoscopic gastric banding . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In all subjects we assessed plasma levels of ghrelin , leptin , soluble leptin receptor , insulin , IGF 1 , IGFBP 1 , IGFBP 3 and IGFBP 6 . ^^^
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In leptin deficient ( lep ( ob ) / lep ( ob ) ) and leptin receptor deficient ( lepr ( db ) / lepr ( db ) ) mice , NPY / AgRP spike frequency was not significantly increased by fasting , and even in mutant mice fed ad libitum , spike frequency was at least as high as in fasted wild type mice . ^^^
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Serum soluble leptin receptor levels were increased in R AN and P AN and unchanged in BN patients . ^^^
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Feedback inhibition of leptin receptor / Jak2 signaling via Tyr 1138 of the leptin receptor and suppressor of cytokine signaling 3 . ^^^ Using cultured cells exogenously expressing the long form of the leptin receptor ( LRb ) or an erythropoietin receptor / LRb chimera , we show that chronic stimulation results in the attenuation of LRb signaling and the establishment of a state in which the receptor is refractory to reactivation . ^^^
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We determined circulating leptin receptor concentrations , bound as well as free leptin concentrations , and body composition in 24 monozygotic ( MZ ) and in 22 dizygotic ( DZ ) twin pairs . ^^^ Bound leptin and leptin receptor concentrations were inversely correlated with body fat content . ^^^ The correlations in age and sex adjusted free leptin , bound leptin , and leptin receptor concentrations were higher between MZ twins than between DZ twins . ^^^ Adjusted heritability ( h 2 ) estimates were 0 . 28 for free leptin , 0 . 73 for bound leptin , and 0 . 55 for leptin receptor . ^^^ The genetic correlation with body fat was 0 . 58 for the leptin receptor , 0 . 20 for bound leptin , and 0 . 93 for free leptin . ^^^
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Pre treatment with excess of unlabelled leptin in vivo revealed a rapid hepatic down regulation of leptin receptor isoforms when tested by in situ hybridization , immunoblotting or immunohistochemistry . ^^^ CONCLUSIONS : The present data support an active role of the liver in the modulation of the leptin signal through different regulation of the soluble leptin receptor , the bound and free forms of the hormone , which may have important implications for leptin ' s central efficacy and the development of ' leptin resistance ' . . ^^^
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Here , we extend these observations to immortalized human lymphoma U 937 cells , where stimulation of FAAH by leptin ( up to approximately 300 % of the controls ) involves binding to a leptin receptor ( Kd = 2 . 0 + / 0 . 1 nm , Bmax = 382 + / 5 fmol . mg protein ( 1 ) , apparent molecular mass of approximately 110 kDa ) , and stimulation by progesterone involves an intracellular receptor of approximately 120 kDa . ^^^ Interestingly , human neuroblastoma CHP 100 cells also have a leptin receptor ( approximately 110 kDa , Kd = 2 . 2 + / 0 . 2 nm , Bmax = 339 + / 8 fmol . mg protein ( 1 ) ) , a progesterone receptor ( approximately 120 kDa ) , STAT 3 and Ikaros , yet their FAAH is not activated by leptin or progesterone . ^^^
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A possible role of neuropeptide Y , agouti related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat . ^^^ Leptin receptor mRNA levels were analysed using RT PCR . ^^^ RESULTS : Perinatally overfed neonatal male rats exhibited hyperleptinaemia and a decrease in hypothalamic mRNA levels of the long isoform of the leptin receptor ( OB Rb ) , explaining their leptin resistance . ^^^ In contrast , perinatally underfed neonatal male rats with hypoleptinaemia showed an increase in hypothalamic mRNA of the short isoforms of the leptin receptor . ^^^
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GALP containing neurons express leptin receptor and contain alpha melanocyte stimulating hormone . ^^^
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The leptin receptor in human osteoblasts and the direct effect of leptin on bone metabolism . ^^^ It is important to elucidate whether the leptin receptor , especially the long signal transducing form of the leptin receptor ( OB Rb ) is expressed in human osteoblasts . ^^^
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The leptin receptor ( LEPR ) is a class 1 cytokine receptor signalling via both the janus kinase / signal transducer and activator of transcription ( JAK / STAT ) and the MAP kinase pathways . ^^^ To enable a detailed analysis of leptin signalling in pancreatic beta cells , LEPR point mutants with single or combined exchanges of the three intracellular tyrosines were expressed in HIT T 15 insulinoma cells . ^^^ Each of the three intracellular tyrosine residues in LEPR exhibited different signalling capacities : Tyr 985 was necessary and sufficient for leptin induced activation of ERK1 / 2 ; Tyr 1077 induced tyrosyl phosphorylation of STAT 5 ; and Tyr 1138 was capable of activating STAT 1 , STAT 3 and STAT 5 . ^^^ Pleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines . ^^^
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Induction of leptin receptor expression in the liver by leptin and food deprivation . ^^^ However , the regulated expression of the leptin receptor ( Ob R ) has not been studied in detail . ^^^ Expression profiling of liver mRNA in leptin treated wild type mice revealed a marked increase in leptin receptor mRNA levels , which had not previously been described . ^^^ This was confirmed by isoform specific real time PCR , which showed a > 25 fold increase in the mRNAs encoding the short forms ( Ob Ra , Ob Rc ) and a > 10 fold increase in the mRNA encoding the long ( Ob Rb ) form of the leptin receptor in liver . ^^^ In parallel , we also observed induction of plasma soluble leptin receptor ( SLR ) protein by leptin administration , pair feeding , and short term food restriction . ^^^
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The aim of this study was to investigate the physiological relevance of leptin ' s signaling of nutritional status by comparing the effects of leptin with the effects of re feeding on fasting induced changes in the expression of the long form of the leptin receptor ( Ob Rb ) , NPY , and CART . ^^^
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Clinical features associated with circulating concentration of soluble leptin receptor in patients with diabetes . ^^^ We aimed to determine if there were any clinical features that were significantly associated with the circulating concentration of soluble leptin receptor ( OB Re ) in 67 Japanese subjects with diabetes mellitus . ^^^
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The diabetes ( db / db ) genotype mutation induces a hyperglycemic hyperinsulinemic endometabolic state in C57BL / KsJ mice , manifesting a type 2 NIDDM diabetes obesity syndrome ( DOS ) in this hyperphagic , leptin receptor ( lf ) defective model . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In the present study , our aim was to determine whether intrafetal glucose infusion increases fetal adiposity , synthesis and secretion of leptin and regulates gene expression of the ' appetite regulatory ' neuropeptides neuropepetide Y ( NPY ) , agouti related peptide ( AGRP ) , pro opiomelanocortin ( POMC ) and cocaine and amphetamine regulated transcript ( CART ) and receptors ( leptin receptor ( OB Rb ) and melancortin 3 receptor ( MC3R ) ) within the fetal hypothalamus . ^^^
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The leptin receptor isoform and intracellular mechanisms involved in regulation of the adrenocortical activity at multiple levels might differ between target tissues ( CNS vs periphery ) and age ( neonates vs adult ) . ^^^
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Inverse changes in the serum levels of the soluble leptin receptor and leptin in neonates : relations to anthropometric data . ^^^ We aimed to evaluate the role of the soluble leptin receptor ( sOB R ) , the major leptin binding protein in blood , for the regulation of growth and development of neonates . ^^^
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Structural characteristics of leptin and the leptin receptor already suggest an immune modulatory function . ^^^
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Fragment Ac [ Ser 117 ] Lep 116 140 NH 2 ( 5 ) induced Fos ir in hypothalamic nuclei that express leptin receptor long form . ^^^
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Leptin signaling primarily depends on the leptin receptor ( Ob R ) . ^^^
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Here we show that p 27 ( Kip 1 ) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 ( Irs 2 ( / ) ) or the long form of the leptin receptor ( Lepr ( / ) or db / db ) . ^^^
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To assess the relative contributions of day / night patterns in behaviors ( sleep / wake cycle and food intake ) and of the endogenous circadian pacemaker on observed day / night patterns of adipokines , in six healthy subjects we measured circulating leptin , soluble leptin receptor , adiponectin , glucose , and insulin levels throughout a constant routine protocol ( 38 h of wakefulness with constant posture , temperature , and dim light , as well as identical snacks every 2 h ) and throughout sleep and fasting periods before and after the constant routine . ^^^
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Differentiated human neuroblastoma ( SH SY5Y ) cells express endogenous ObR and IR , and respond to leptin and insulin with stimulation of STAT 3 and MAPK ( mitogen activated protein kinase ) phosphorylation , and PI3K activity . ^^^
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An fa allele of the leptin receptor gene ( Lepr ( fa ) ) of the Zucker fatty rat was introduced into the genome of the Spontaneously Diabetic Torii ( SDT ) rat , an inbred model of nonobese type 2 diabetes mellitus , through the ' Speed congenic method ' . ^^^
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Polymorphisms of leptin receptor ( LEPR ) may contribute to a common form of obesity and , as a consequence , obesity related diseases . ^^^ We evaluated anthropometric measurements , blood pressure , seric glucose , insulin , leptin levels , heart sympathetic activity ( by electrocardiograph monitoring at rest ) , and the Gln223Arg and Pro1019Pro LEPR polymorphisms in each subject . ^^^ Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene , and traits related to obesity in Mexican adolescents . ^^^
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This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue ( sWAT ) of an obese patient with a leptin receptor deficiency . ^^^ MATERIALS AND METHODS : Gene expression profiling was performed in the sWAT of two extremely obese patients with a leptin receptor deficiency . ^^^
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We explored whether the intrahippocampal administration of insulin or leptin improved spatial memory formation in rats following a radial maze task and whether the insulin and leptin receptor expression in different areas of the hippocampus was affected . ^^^ The application of insulin increased the expression of the long form of the leptin receptor in the Ammon ' s horn and dentate gyrus region of the hippocampus in the learning group only . ^^^ These data clearly show that learning is a prerequisite for the effect of insulin on leptin receptor expression . . ^^^
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RT PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium . ^^^ Furthermore , immunocytochemistry demonstrated that the long form leptin receptor protein ( ObRb ) is present in human coronary endothelium . ^^^
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Leptin ' s actions are mediated via the long form of its receptor , Ob Rb , but access to this receptor on target cells is also influenced by truncated leptin receptor isoforms Ob Ra and Ob Re . ^^^
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Leptin receptor action and mechanisms of leptin resistance . ^^^
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BACKGROUND INFORMATION : Leptin , an adipocyte secreted hormone , signals through activation of its membrane embedded receptor ( LEPR ) . ^^^ Quantitative FRET imaging of leptin receptor oligomerization kinetics in single cells . ^^^
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Three non synonymous single nucleotide polymorphisms ( T221C , T232A and C233T ) were detected in exon 4 of the porcine leptin receptor ( LEPR ) gene . ^^^
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A twin study for serum leptin , soluble leptin receptor , and free insulin like growth factor 1 in pubertal females . ^^^ OBJECTIVE : To determine the genetic and environmental influences to the variations of basal leptin , soluble leptin receptor ( SOB R ) , free leptin index ( FLI ) , and free IGF 1 levels in pubertal females . ^^^
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Leptin receptor expression was measured by in situ hybridization with pan leptin receptor probes and by immunoblotting . ^^^ At baseline , all forms of the leptin receptor were markedly to completely down regulated in DIO rats . ^^^
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T cell lines against human myelin basic protein ( hMBP ) produced immunoreactive leptin and up regulated the expression of the leptin receptor ( ObR ) after activation with hMBP . ^^^ Treatment with either anti leptin or anti leptin receptor neutralizing antibodies inhibited in vitro proliferation in response to hMBP . ^^^ To better analyze the finding , we enumerated T ( Regs ) in leptin deficient ( ob / ob ) and leptin receptor deficient ( db / db ) mice and observed the significant increase in T ( Regs ) . ^^^
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The inbred mouse strain C57BLKS / J ( BKS ) carrying a mutation of the leptin receptor lepr ( / ) ( BKS db ) is a classic mouse model of type 2 diabetes . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin and soluble leptin receptor levels in obese children in fasting and satiety states . ^^^ Leptin and soluble leptin receptor levels were measured in fasting and satiety states . ^^^ RESULTS : Serum leptin levels were significantly higher and soluble leptin receptor levels were significantly lower in obese children compared to controls in fasting and satiety states . ^^^ In obese children , there was a high and inverse correlation between leptin levels and soluble leptin receptor levels after fasting . ^^^ CONCLUSION : In this study , being the first to consider both fasting and satiety states , obese children were found to have higher leptin , but lower soluble leptin receptor levels , compared to controls . ^^^
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We measured serum concentrations of leptin , soluble leptin receptor , insulin , ghrelin , and thyroid hormones [ thyrotropin , triiodothyronine ( T ( 3 ) ) , and thyroxine ] ; fat mass ( FM ) and fat free mass ( FFM ) ; resting energy expenditure ( REE ) ; energy intake ; and eating behavior . ^^^
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The soluble leptin receptor in olanzapine induced weight gain : results from a prospective study . ^^^
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Upon leptin binding , the leptin receptor is activated , leading to stimulation of the JAK / STAT signal transduction cascade . ^^^
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Furthermore , there was a dose and time dependent increase in the phosphorylation of STAT 1 and STAT 3 , indicating that Ob R ( b ) ( the long form of the leptin receptor ) expressed by the keratinocytes is functional . ^^^
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Although there is some controversy surrounding the data , they are supported by the presence of leptin receptor mRNA in mouse and human oocytes and embryos throughout preimplantation development . ^^^ Given that expression of the leptin receptor increases in the human endometrium during the luteal phase , the secreted leptin could trigger its activation . ^^^ Finally , leptin and the leptin receptor have been detected in implantation sites . ^^^
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A total of 283 SNP were discovered in 31 897 base pairs ( bp ) from 12 genes of the growth hormone ( GH ) , growth hormone receptor ( GHR ) , ghrelin , growth hormone secretagogue receptor ( GHSR ) , insulin like growth factor 1 and 2 ( IGF 1 and 2 ) , insulin like growth factor binding protein 2 ( IGFBP 2 ) , insulin , leptin receptor ( LEPR ) , pituitary specific transcription factor 1 ( PIT 1 ) , somatostatin ( SS ) , thyroid stimulating hormone beta subunit ( TSH beta ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance . ^^^ The leptin receptor ( OB R ) gene is a promising candidate gene for type 2 diabetes , because leptin and its receptor play an important role in insulin secretion and the development of obesity . ^^^
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The extent of ossification of posterior longitudinal ligament of the spine associated with nucleotide pyrophosphatase gene and leptin receptor gene polymorphisms . ^^^ OBJECTIVE : To analyze whether polymorphisms of the nucleotide pyrophosphatase ( NPPS ) gene and the leptin receptor gene predispose to an increased frequency and severity of OPLL . ^^^ The Zucker fatty rat , another animal model for OPLL , has a missense mutation in the leptin receptor gene . ^^^ Polymorphisms of the NPPS gene and the leptin receptor gene were analyzed using the PCR assay . ^^^ RESULTS : No significant association was found between the polymorphisms and the existence of OPLL in both the NPPS and the leptin receptor genes . ^^^
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Leptin receptor activation depends on critical cysteine residues in its fibronectin type 3 subdomains . ^^^ The leptin receptor ( LR ) complex is composed of a single subunit belonging to the class 1 cytokine receptor family and exists as a preformed complex . ^^^
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Mapping leptin interacting sites in recombinant leptin binding domain ( LBD ) subcloned from chicken leptin receptor . ^^^ The binding domain of the chicken leptin receptor [ chLBD ( chicken leptin binding domain ) ] , subcloned from the full size chicken leptin receptor and prepared in an Escherichia coli system , was subjected to site directed mutagenesis to identify the amino acids involved in leptin binding . ^^^
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Leptin receptor expression and in vitro leptin actions on prostaglandin release and nitric oxide synthase activity in the rabbit oviduct . ^^^ In this study , we have examined the presence and the distribution of receptors for leptin ( Ob R ) in the oviduct of rabbits , and the effects of leptin on the release of prostaglandin ( PG ) F2alpha and PGE 2 and on the activity of nitric oxide ( NO ) synthase ( NOS ) by oviducts cultured in vitro . ^^^
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OBJECTIVE : To study the leptin receptor isoforms regulation by leptin and insulin . ^^^ Using the semi quantitative RT PCR technique , the mRNA expressions of long ( OB Rb ) and short ( OB Ra : OB R219 . 3 ) leptin receptor isoforms were measured . ^^^
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We demonstrated that long and short isoforms of the leptin receptor and intracellular proteins mediating leptin signaling were expressed in human heart by RT PCR , immunocytochemistry , or both methods . ^^^
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This hyperleptinaemia , despite leptin receptor expression in tumours , did not induce significant variation in tumour volume or weight . ^^^
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The diabetes ( db / db ) genotype mutation induces a hyperglycemic hyperinsulinemic endometabolic state in C57BL / KsJ mice , manifesting a type 2 NIDDM diabetes obesity syndrome ( DOS ) associated with intrinsic leptin receptor expression defects . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor system of human platelets . ^^^ The current study examines the effect of leptin on human platelets , and provides initial insights into the nature of the leptin receptor on these platelets . ^^^ Western blotting and reverse transcriptase polymerase chain reaction ( RT PCR ) experiments showed that platelets from both groups only express the signaling form of the leptin receptor , and that responder platelets express higher levels of this receptor than non responders . ^^^ These preliminary studies demonstrate that platelets are a major source of leptin receptor in the circulation , and suggest that leptin responsive individuals may have a higher risk for obesity associated thrombosis than non responsive individuals . . ^^^
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To test the degree of functional neuronal leptin signaling required for the maintenance of body composition , fertility , and cold tolerance , transgenic mice expressing Cre in neurons ( CaMKIIalpha Cre ) were crossed to mice carrying a floxed leptin receptor ( Lepr ) allele to generate mice with neuron specific deletion of Lepr in approximately 50 % ( C F / F mice ) and approximately 75 % ( C Delta17 / F mice ) of hypothalamic neurons . ^^^ Leptin receptor ( LEPR ) deficient mice ( Delta17 / Delta17 ) with heat shock Cre mediated global Lepr deletion served as obese controls . ^^^ Significant increases in total fat mass ( C F / F : P < 0 . 01 ; C Delta17 / F and Delta17 / Delta17 : P < 0 . 001 vs . sex matched , lean controls ) , and serum leptin concentrations ( P < 0 . 001 vs . controls ) were present in proportion to Lepr deletion . ^^^ These findings support the hypothesis that body weight , adiposity , serum leptin concentrations , and glucose intolerance are proportional to hypothalamic LEPR deficiency . ^^^
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Considerable leptin receptor expression was observed in the milk producing epithelial cells , which is the same cell type that produces most of the udder leptin . ^^^
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Leptin mediated activation of human platelets : involvement of a leptin receptor and phosphodiesterase 3A containing cellular signaling complex . ^^^ Using pharmacological , biochemical , and cell biological approaches , we show that leptin induced platelet activation required activation of a signaling cascade that included the long form of the leptin receptor , three kinases [ Janus kinase 2 ( JAK 2 ) , phosphatidylinositol 3 kinase ( PI3K ) , and protein kinase B ( PKB / Akt ) ] , the insulin receptor substrate 1 ( IRS 1 ) , and the major human platelet cAMP phosphodiesterase phosphodiesterase 3A ( PDE3A ) . ^^^
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Quantitative , real time PCR revealed no significant difference in coronary artery leptin receptor gene expression between control and high fat fed dogs . ^^^ The resistance is not due to altered endothelium dependent or independent coronary dilation , increased endothelium derived hyperpolarizing factor , or changes in coronary leptin receptor mRNA levels . . ^^^
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We previously reported a positive association among body mass index , single nucleotide polymorphisms ( SNP ) in the leptin and leptin receptor genes that are involved in body weight regulation , and non Hodgkin lymphoma ( NHL ) . ^^^
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Previously we have reported that both leptin and leptin receptor are essential for apoM expression in vivo . ^^^ The expression of apoM is lower in the leptin deficient ( ob / ob ) mouse and leptin receptor deficient ( db / db ) mouse than in the normal mouse . ^^^
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Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat . ^^^ Real time RT PCR was used to determine levels of mRNA for the various leptin receptor isoforms in a number of microdissected hypothalamic nuclei and the choroid plexus . ^^^ To investigate the functional activation of the leptin receptor , immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 ( pSTAT 3 ) was examined in the arcuate nucleus and the ventromedial nucleus of the hypothalamus ( VMH ) of fasted diestrous and d 14 pregnant rats after an intracerebroventricular ( i . c . v . ) injection of either leptin ( 4 mug ) or vehicle . ^^^
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We demonstrated the presence of leptin receptor in human immature and mature DCs both at mRNA and protein level and its capacity to transduce leptin signaling leading to STAT 3 phosphorylation . ^^^
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Leptin significantly decreased the expression of its receptor ( Ob R ) , neuropeptide Y ( NPY ) , orexin ( ORX ) , and orexin receptor ( ORXR ) ( P < 0 . 05 ) , but not that of agouti related protein ( AgRP ) ( anabolic / orexigenic effectors ) in chicken hypothalamus . ^^^
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In all subjects , we further assessed the concentrations of leptin , soluble leptin receptor , insulin , IGF 1 , free IGF 1 and IGFBP 1 , 2 , 3 and 6 . ^^^
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Research for development of pharmacologic antagonism for the leptin receptor is currently under way . ^^^
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Interaction effects between PTPN 1 and leptin receptor gene variants influenced insulin sensitivity index and AIR ( glucose ) ( p from 0 . 006 to 0 . 010 ) . ^^^ Gene gene interactions between the PTPN 1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity . ^^^
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METHODS AND RESULTS : Here it is shown that angiogenic repair of ischemic hindlimbs was impaired in Lepr ( db / db ) mice , a leptin receptor deficient model of diabetes , compared with wild type ( WT ) C57BL / 6 mice , as evaluated by laser Doppler flow and capillary density analyses . ^^^
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Mapping of the interface between leptin and the leptin receptor CRH 2 domain . ^^^ The extracellular domain of the leptin receptor consists of two cytokine receptor homology ( CRH ) domains separated by an immunoglobulin like domain , and followed by two juxtamembrane fibronectin type 3 modules . ^^^
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Although the leptin receptor ( LR ) has not been found on GnRH neurons , leptin stimulates the release of GnRH from rat and porcine hypothalamic explants . ^^^
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During pubertal development serum leptin levels , hypothalamic leptin receptor mRNA and estrogen induced leptin gene expression in fat increased with age and adiposity in the pig and this occurred at the time of expected puberty . ^^^
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This study was performed to get insight into the function of leptin during the periparturient period and to perform an association study between polymorphisms in the bovine leptin gene and leptin receptor gene and fertility as well as production traits . ^^^
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Changes in expression of the genes for the leptin receptor and the growth hormone releasing peptide / ghrelin receptor in the hypothalamic arcuate nucleus with long term manipulation of adiposity by dietary means . ^^^ We measured expression of the leptin receptor ( Ob Rb ) and the ghrelin / growth hormone releasing peptide receptor ( GHS R ) in the arcuate nucleus of sheep held at either high or low levels of adiposity . ^^^
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Specific leptin receptor mRNA , both short and long isoform transcripts , were identified in SK N MC cells by RT PCR . ^^^ In conclusion , ( 1 ) human SK N MC neuroepithelioma cells express ob and leptin receptor mRNA and secrete leptin . ( 2 ) Added exogenous leptin does not affect IGF 1 , IGFBP 2 or IGF 1 receptor mRNA expression and IGF 1 and IGFBP 2 secretion by SK N MC cells in vitro under the conditions studied . ^^^
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These changes were accompanied by a significant down regulation of leptin receptor gene expression , however SREBP 1 , the main transcription factor of lipogenic genes , remained unchanged . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Common leptin receptor polymorphisms do not modify the effect of alcohol ingestion on serum leptin levels in a controlled feeding and alcohol ingestion study . ^^^ We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms , K109R ( Lys109Arg ) , Q223R ( Gln223Arg ) , S343S [ Ser ( T ) 343Ser ( C ) ] , and K656N ( Lys656Asn ) , of reported physiologic significance during a controlled intervention . ^^^ No significant effects were found between common leptin receptor polymorphisms and serum leptin levels ( P > or = 0 . 26 ) . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Apoptotic pathways are inhibited by leptin receptor activation in neutrophils . ^^^ The antiapoptotic effects of leptin were concentration dependent and blocked by an anti leptin receptor mAb . ^^^
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Insulin alone down regulated the leptin signaling pathway , JAK 2 association with ObR decreased at all time points , and JAK 2 phosphorylation decreased similarly . ^^^ Leptin alone also appeared to down regulate JAK 2 association with the ObR , but stimulated the down regulated pathway to signal , JAK 2 tyrosine phosphorylation being increased at later time points . ^^^ Pretreatment with leptin followed by insulin time course showed marked up regulation of the early leptin signaling pathway , JAK 2 association with the ObR being increased by insulin while JAK 2 tyrosine phosphorylation was also increased . ^^^
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Leptin receptor and functional effects of leptin in human endothelial progenitor cells . ^^^ The presence of the leptin receptor and the functional effects of leptin in EPCs were investigated . ^^^ The presence of the long form of the leptin receptor in EPCs was confirmed by Western blotting and with immunofluorescence . ^^^ In summary , the leptin receptor is present in human EPCs and leptin may affect EPC function , both in physiological and in hyperleptinemic conditions . ^^^
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Using a sensitive hydrophobic cluster analysis of leptin ' s and LEPR ' s sequences , we identified hydrophobic stretches in leptin ' s A B loop ( amino acids 39 42 ) and in the N terminal end of LEPR ' s IGD ( amino acids 325 328 ) that are predicted to participate in site 3 and to interact with each other in a beta sheet like configuration . ^^^ All muteins acted as true antagonists , i . e . they bound LEPR with an affinity similar to the wild type hormone , had no agonistic activity and specifically inhibited leptin action in several leptin responsive in vitro bioassays . ^^^ Alanine mutagenesis of LEPR ' s IGD ( amino acids 325 328 ) drastically reduced its biological but not binding activity , indicating the importance of this region for interaction with leptin ' s site 3 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Directional secretion and transport of leptin and expression of leptin receptor isoforms in human placental BeWo cells . ^^^ Additionally , the effects of dexamethasone on transcellular passage of leptin across BeWo monolayers , and on expression of the leptin receptor isoforms Ob Rs and Ob RL were examined . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Transcript levels of the genes encoding leptin receptor ( LEPR ) , signal transducer and activator of transcription ( STAT 3 ) , BCL 2 associated 10 protein ( BAX ) , and baculoviral inhibitor of apoptosis protein repeat containing 4 ( BIRC 4 , also known as XIAP ) , were determined by reverse transcriptase quantitative polymerase chain reaction analysis of expanded and hatched blastocysts . ^^^ Depending on the dose used , leptin treatment of oocytes resulted in increased LEPR , STAT 3 , and BIRC 4 mRNA levels and reduced BAX mRNA levels in blastocysts . ^^^ In conclusion , leptin improved the ability of the oocyte to sustain embryonic development and had long term effects on blastocyst apoptosis and transcript abundance of LEPR , STAT 3 , and apoptosis associated genes . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Relationship between soluble leptin receptor , leptin , lipid profiles and anthropometric parameters in overweight and obese Thai subjects . ^^^ Median , range and 95 % confidence interval ( CI ) for median of age , anthropometric variables , soluble leptin receptor , serum leptin and lipid profile levels of 48 overweight ( Body mass index ( BMI ) = 25 . 00 29 . 99 kg / m2 ) and obese ( BMI > or = 30 . 00 kg / m2 ) Thai males and 166 overweight and obese Thai females , compared with 26 males and 81 females in a control group ( BMI = 18 . 50 24 . 99 kg / m2 ) , were determined The study subjects were persons who turned up regularly for physical check ups at the Out patient Department , General Practice Section , Ratchawithi Hospital , Bangkok , aged between 18 60 years . ^^^ Soluble leptin receptor and HDL C were significantly lower in the overweight and obese males and females . ^^^ Low soluble leptin receptor levels were found in 38 . 1 % ( 8 / 21 ) of the overweight and obese males , while 31 . 5 % ( 29 / 92 ) were found in the overweight and obese females . ^^^ Both low soluble leptin receptor levels and elevated leptin levels were found in 9 . 5 % ( 2 / 21 ) and 29 . 4 % ( 27 / 92 ) of the overweight and obese males and females , respectively . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Some polymorphic genes involved in the regulation of leptin the leptin gene ( LEP A19G ) , the leptin receptor gene ( LEPR Q223R , K109R , and K656N ) , and the peroxisome proliferator activated receptor gamma gene ( PPARG P12A and C161T ) have been investigated as possible factors associated with obesity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We measured plasma insulin , adipokines ( leptin , adiponectin , resistin , tumor necrosis factor [ TNF ] alpha , interleukin [ IL ] 6 ) , soluble leptin receptor ( sOb R ) , the main leptin binding protein , and C reactive protein ( CRP ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Relationship between serum concentrations of leptin , soluble leptin receptor , testosterone and IGF 1 , and growth during the first year of postnatal life in the male rhesus monkey , Macaca mulatta . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
On the other hand , leptin receptor ( long and short forms ) immunolabelings , although absent in the gastric epithelial cell plasma membranes , were present in enterocytes at the level of their apical and basolateral membranes . ^^^ Duodenal , jejunal , and ileal enterocytes displayed similar labelings for the leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Obese mice without leptin ( ob / ob ) or the leptin receptor ( db / db ) have increased plasma HDL levels and accumulate a unique lipoprotein referred to as LDL / HDL1 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Circulating soluble leptin receptor , leptin , and insulin resistance before and after weight loss in obese children . ^^^ OBJECTIVE : To study the relationships between leptin , soluble leptin receptor ( sOB R ) , and insulin resistance in obese children before and after weight reduction . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
OBJECTIVE : Genetic variation in leptin receptor ( LEPR ) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations . ^^^ Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight : The Finnish Diabetes Prevention Study . ^^^ CONCLUSION : Two polymorphisms ( Lys109Arg , Gln223Arg ) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high risk individuals with IGT . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In these cells , the NPY gene was transactivated by leptin through activation of leptin receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin plays an important role in the regulation of body fat homeostasis , and potential associations of leptin receptor gene ( LEPR ) polymorphisms with obesity have been suggested . ^^^ By direct sequencing , we investigated four leptin receptor gene ( LEPR ) polymorphisms at codons 109 , 223 , 656 , and 1019 . ^^^ Our results indicate that it is difficult to explain breast cancer on the basis of serum leptin concentrations or polymorphisms in the LEPR gene . . ^^^ Relationships among serum leptin , leptin receptor gene polymorphisms , and breast cancer in Korea . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The present study was designed to ascertain whether ( 1 ) lizard thyroid gland expresses the long form of leptin receptor ( Ob Rb ) and ( 2 ) the leptin administration affects the thyroid gland activity in this species ( and to verify whether leptin plays a similar role in reptiles as observed in the other vertebrates ) . ^^^ The presence of leptin receptor in the thyroid gland of Podarcis sicula was demonstrated by immunohistochemical technique ( avidin biotin peroxidase complex ABC method ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
OBJECTIVE : The purpose of this study was to determine the influence of reduced uteroplacental perfusion pressure on plasma leptin and placental leptin receptor expression in rats that develop hypertension in the third trimester of pregnancy . ^^^ Maternal plasma leptin levels , placental leptin receptor abundance , fetal number , fetal weight , and placental weight were determined . ^^^ Maternal systolic blood pressure and leptin receptor protein abundance was increased in the experimental group . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The differential amounts of leptin and Ob R isoforms suggested a role for leptin in such endometrial issues as blastocyst implantation . ^^^
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AAV mediated leptin receptor installation improves energy balance and the reproductive status of obese female Koletsky rats . ^^^ Koletsky ( f / f ) rats with a leptin receptor ( OB Rb ) gene mutation are obese , diabetic and infertile . ^^^ These studies show that long term installation of a functional leptin receptor in the CNS is achievable using rAAV vectors and further show that leptin acts on specific sites in the brain to produce differential effects on food intake , energy expenditure and reproduction . . ^^^
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However , since the RIP Cre transgene is also expressed in the hypothalamus , and thereby Stat 3 was deleted from neurons expressing the leptin receptor , it was not clear as to which of the metabolic defects were due to the loss of Stat 3 from beta cells or the hypothalamus . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor has been identified in endothelial cells . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
ObRa and ObRe are differentially expressed in adipose tissue in aged food restricted rats : effects on circulating soluble leptin receptor levels . ^^^ In rodents , soluble leptin receptor ( SLR ) may be generated by alternative splicing of ObR mRNA and / or as a cleavage product of ObR membrane anchored receptors . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
METHODS : Receptors of bombesin 3 , cholecystokinin ( CCK ) A , CCK B , glucagon like peptide ( GLP ) 1 , melanin concentrating hormone ( MCH ) 1 , orexin 1 , orexin 2 , neuromedin B , neuropeptide Y ( NPY ) 1 and NPY 5 , neurotensin ( NT ) 1 , NT 2 , NT 3 , and leptin receptor long form mRNA in GT 1 7 cells were detected by reversed transcriptase polymerase chain reaction . ^^^ RESULTS : Receptors of bombesin 3 , CCK B , GLP 1 , MCH 1 , orexin 1 , neuromedin B , NPY 1 , NPY 5 , NT 1 , NT 3 , and leptin receptor long form mRNA were expressed in GT 1 7 cells , of which , receptors of GLP 1 , neuromedin B , NPY 1 , and NT 3 were highly expressed . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Increased hypercholesterolemia and atherosclerosis in mice lacking both ApoE and leptin receptor . ^^^ In this study , we investigated the effect of the deletion of the long form leptin receptor on the progression of atherosclerosis in ApoE / mouse . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
These findings were confirmed from the observations that the long isoform of the leptin receptor , which is capable of signal transduction , was present only in kindled , but not in control rats . ^^^
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Besides , tyrosine phosphorylation of Sam 68 allows the formation of signalling complexes with other proteins containing SH 2 and SH 3 domains , suggesting a role in signal transduction of different systems in human lymphocytes , such as the T cell receptor , and leptin receptor , or the insulin receptor in other cell types . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To assess the physiological significance of leptin signaling in the ARH , we used mice homozygous for a FLPe reactivatable , leptin receptor null allele ( Lepr ( neo / neo ) mice ) . ^^^ We found that unilateral restoration of leptin signaling in the ARH of Lepr ( neo / neo ) mice leads to a modest decrease in body weight and food intake . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Roles for leptin receptor / STAT3 dependent and independent signals in the regulation of glucose homeostasis . ^^^ Leptin activates the long form of the leptin receptor ( LRb ) to control feeding and neuroendocrine function and thus regulate adiposity . ^^^
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Moreover , leptin receptor Ob Rb expression in the hypothalamus was up regulated in SAMP 8 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
This study was carried out to investigate the changes of orexin A ( OXA ) and neuropeptide Y ( NPY ) expression in the hypothalamus of the obese and lean Zucker Diabetic Fatty ( ZDF ) rats which have a missense mutation in the leptin receptor gene . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The influence of very low calorie diet on serum leptin , soluble leptin receptor , adiponectin and resistin levels in obese women . ^^^ VLCD significantly decreased BMI , HOMA index , serum glucose , insulin and leptin levels and increased soluble leptin receptor levels . ^^^ We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Lack of correlation between leptin receptor expression and PI 3 K / Akt signaling pathway proteins immunostaining in endometrioid type endometrial carcinomas . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The leptin receptor gene ( LEPR ) is a candidate for traits related to growth and body composition , and is located on SSC 6 in a region where fatness and meat composition quantitative trait loci ( QTL ) have previously been detected in several F 2 experimental designs . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Serum leptin , soluble leptin receptor , free leptin index and bone mineral density in patients with primary biliary cirrhosis . ^^^ We investigated the relationship between serum leptin levels , soluble leptin receptor ( sOB R ) , free leptin index ( FLI ) and BMD in patients with primary biliary cirrhosis ( PBC ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In the present study , we found that db / db mice on the FVB genetic background with loss of function mutation of the leptin receptor ( FVB Lepr ( db ) mice or FVBdb / db ) develop severe diabetic nephropathy , including glomerulosclerosis , tubulointerstitial fibrosis , increased expression of type 4 collagen and fibronectin , and proteinuria , which is associated with increased renal mRNA abundance of transforming growth factor beta , plasminogen activator inhibitor 1 , and vascular endothelial growth factor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of agouti related peptide , neuropeptide Y , pro opiomelanocortin and the leptin receptor isoforms in fetal mouse brain from pregnant dams on a protein restricted diet . ^^^ Expression of agouti related peptide , neuropeptide Y , pro opiomelanocortin and leptin receptor isoforms were found in fetal mouse brain at embryonic day 12 ( E 12 ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Expression of leptin receptor and suppressor of cytokine signaling 3 genes in adenohypophysis of normal fed and fasted cows . ^^^ Expression of leptin receptor ( LR ) and suppressor of cytokine signaling ( SOCS ) 3 genes was investigated in normal fed and fasted cows . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Given that the deregulated expression of a variety of growth factors and / or their receptors has been implicated in the pathogenesis of certain leukemias , we aimed to characterize the potential differences in the expression pattern of the two major leptin receptor transcript variants in peripheral blood mononuclear cells ( PBMC ) between different hematologic malignancies . ^^^ Serum leptin levels and circulating soluble leptin receptor levels were slightly but not significantly higher in AML and MDS . ^^^ These alterations in the expression of the leptin receptor isoforms in MDS and AML patients could suggest a potential role of leptin and its signaling in hematopoietic malignancies , which requires further examination . . ^^^ Using RT PCR and Southern blotting , we compared the expression levels of the two major leptin receptors , the longest ( OB R ( L ) ) and the shortest ( OB R ( S ) ) splice variants , in PBMC from patients with myelodysplastic syndrome ( MDS ) , acute myeloid leukemia ( AML ) , healthy individuals and two human hematopoietic cell lines ( HL 60 and K 562 ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin receptor belongs to the class 1 cytokine receptor superfamily . ^^^ At least five isoforms of leptin receptor exist , primarily because of alternate splicing . ^^^ In this review , we present the crystal structure of leptin and the structural comparison with other four helical cytokines , discuss the leptin receptor binding models based on other cytokine receptor complex structures , and summarize the most recent progress on leptin signal transduction pathways especially its link to peripheral lipid metabolism through AMP activated protein kinase and hepatic stearoyl CoA desaturase 1 pathways . ^^^
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A spontaneous single base mutation in the leptin receptor of type 1 diabetes prone NOD / LtJ mice ( designated as Lepr ( db 5J ) ) produced a glycine640valine transversion in the extracellular domain . ^^^ Novel leptin receptor mutation in NOD / LtJ mice suppresses type 1 diabetes progression : 1 . ^^^ These results indicated that the manipulation of the leptin / leptin receptor axis may provide a novel means of downregulating autoimmunity in type 1 diabetes and confirmed a role for leptin as a mediator in the development of this disease in NOD mice . . ^^^
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Single nucleotide polymorphism analysis in chicken leptin receptor exon 9 ] . ^^^ Leptin receptor is a type 1 cytokine super family member and plays an important role in leptin functioning signal transduction . ^^^
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The leptin leptin receptor system might be up regulated in the airways of chronic obstructive pulmonary disease ( COPD ) . ^^^ In bronchial biopsies obtained from normal subjects and smokers , with and without COPD , the present study examined leptin and leptin receptor expression and their co localisation in airway and inflammatory cells . ^^^ Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end labelling techniques , apoptosis in airway and inflammatory cells and in leptin and leptin receptor expressing cells was investigated . ^^^ In the epithelial cells both leptin and leptin receptor expression was higher in normal subjects than in smokers and COPD subjects . ^^^ In smokers , apoptosis was found in some inflammatory cells , whereas in COPD inflammatory cells , leptin and leptin receptor positive cells were not apoptotic . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Long form leptin receptor mRNA expression in the hypothalamus and pituitary during early pregnancy in the pig . ^^^ OBJECTIVE : The aim of this study was the detection and location of long form leptin receptor ( OB Rb ) in different area of hypothalamus and pituitary in the pig during early pregnancy . ^^^
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Leptin added to culture medium of gastrointestinal explants from 10 to 12 wk old fetuses appeared to affect DNA synthesis as compared with controls , indicating that leptin receptor functionality was developing . ^^^
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Stretching the RPV significantly up regulated leptin production by greater than 100 fold and leptin receptor expression by up to 10 fold . ^^^
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Genetic variants in the leptin ( LEP 19G > A , LEP 2548G > A ) and leptin receptor genes ( LEPR 223Q > R ) , previously shown to modulate NHL risk , as well as a polymorphism in the energy regulatory gene adiponectin ( APM 1 276G > T ) , were investigated . ^^^
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Phosphoinositide 3 kinase ( PI 3 kinase ) has been shown to link leptin receptor activation to stimulation of large conductance Ca2+ activated K+ ( BK ) channels and subsequent inhibition of hippocampal epileptiform like activity . ^^^
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As the indicators of insulin resistance in the local glomerular cells , levels of glucose transporter 1 , leptin receptor , peroxisome proliferator activated receptor gamma , and vascular endothelial growth factor increased , too . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Hormonal regulation of leptin receptor expression in primary cultures of porcine hepatocytes . ^^^ A study was conducted to elucidate hormonal control of leptin receptor gene expression in primary cultures of porcine hepatocytes . ^^^ Leptin receptor expression was calculated relative to co amplified 18S rRNA . ^^^ Expression of the long form of the leptin receptor was confirmed under basal conditions . ^^^ Insulin , glucagon and synthetic human proteins ( ghrelin and GLP 1 ) at 100 ng / ml had no influence on leptin receptor expression ; the addition of T 3 was associated with a marked increase ( P < 0 . 001 ) in expression of total and long forms of the leptin receptor by 1 . 6 and 2 . 4 fold , respectively . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The cell lines express the Ob Rb leptin receptor neuropeptide Y ( NPY ) Y 1 , Y 2 , Y 4 , Y 5 receptors , melanocortin 4 receptor , insulin receptor , and the NT receptor . ^^^
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Both gastric cancer cells expressed leptin and its receptors ( Ob R ) at the protein level . ^^^
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Leptin and leptin receptor expression in skeletal muscle and adipose tissue in response to in vivo porcine somatotropin treatment . ^^^ The present study was performed to examine the response of leptin and leptin receptor ( Rb ) genes to porcine somatotropin ( pST ) stimuli in finishing pigs . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
OBJECTIVE : We examined the associations between polymorphisms in the LEP and leptin receptor ( LEPR ) genes and resting metabolic rate ( RMR ) and respiratory quotient ( RQ ) in the Quebec Family Study . ^^^ Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Qubec Family Study . ^^^
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The present study was designed to address this issue by using obese ( Lepr ( fa ) / Lepr ( fa ) ) Zucker rats , a rat model of genetic leptin receptor deficiency . ^^^ Leptin receptor deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia . ^^^
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Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice , bound to a protein corresponding to the extracellular domain of the leptin receptor . ^^^ Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum Golgi granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells . ^^^ The long form membrane leptin receptor OB Rb , the protease activator furin , and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells . ^^^ Endocrine cells , on the other hand , generate a soluble leptin receptor by mechanisms different from those of the exocrine cells . . ^^^
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Choroid plexus epithelial cells co express the long and short form of the leptin receptor . ^^^ The Ob Ra , also called short form of leptin receptor , and the Ob Rb , which is functionally coupled to intracellular signalling pathways . ^^^ Two types of leptin receptors ( Ob R ) are structurally and functionally characterized . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin exerts insulin sensitizing effects , but obesity has been linked to leptin resistance and low levels of circulating leptin receptor , indicating that high levels of leptin can not mediate its beneficial effects . ^^^
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The steroid hormones are linked to the regulation of leptin and the leptin receptor and probably interact with other pregnancy specific , serum borne factors to regulate leptin dynamics during pregnancy . ^^^
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Leptin and leptin receptor expression in the myometrium and uterine myomas : Is leptin involved in tumor development . ^^^
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We propose that the central leptin resistance resides between leptin receptor and melanocortin receptor activation . ^^^
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We have generated mice that carry a neuron specific leptin receptor ( LEPR ) transgene whose expression is driven by the rat synapsin 1 promoter synapsin LEPR B ( SYN LEPR B ) . ^^^
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Further studies on leptin and leptin receptor expression in myometrium and uterine myomas . ^^^ Expression of the leptin gene and leptin receptor gene was tested in the myometrium of healthy women , and in myomas and the surrounding myometrium of women with benign tumors . ^^^ METHODS : Using RT PCR , expression of the leptin gene and leptin receptor gene were studied in myomas and in the surrounding myometrium in 30 women with uterine myomas at various phases of the menstrual cycle , and in the myometrium of ten women in a control group . ^^^ Presence of leptin gene proteins and leptin receptor gene proteins in the women was also examined by Western blotting . ^^^ The results were confirmed by Western blotting , which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Immunohistochemical evidence of functional leptin receptor expression in neuronal and endothelial cells of the rat brain . ^^^
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Obese mice and rats , which have leptin receptor deficiency , have impaired spatial learning . ^^^
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The aim of this study was to investigate the expression and function of leptin receptors ( ObR ) in human HSCs and the biological actions regulated by leptin . ^^^ Exposure to leptin increased the tyrosine kinase activity of ObR immunoprecipitates and resulted in activation of signal transducer and activator of transcription 3 . ^^^ In conclusion , ObR activation in HSCs leads to increased expression of proinflammatory and proangiogenic cytokines , indicating a complex role for leptin in the regulation of the liver wound healing response . . ^^^
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The ovarian expression of mRNAs for aromatase , IGF 1 receptor , IGF binding protein 2 , 4 and 5 , leptin and leptin receptor in cycling ewes after three days of leptin infusion . ^^^ An experiment was carried out to determine the pattern of follicular expression of mRNAs for aromatase , IGF 1 receptor ( IGF IR ) , IGF binding protein ( IGFBP ) 2 , 4 and 5 , leptin and the long form of the leptin receptor ( Ob Rb ) in ten ewes infused with human recombinant leptin ( n = 5 ; 1 microg / h ) or saline ( n = 5 ) for 72 h in the luteal phase of the oestrous cycle . ^^^
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In 6 days of a HFD , mRNA of the postreceptor leptin inhibitor , suppressor of cytokine signaling 3 , increased 22 fold in WAT , while leptin receptor ( Lepr b ) mRNA gradually disappeared , implying leptinergic blockade at both postreceptor and receptor levels . ^^^
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In the present study , serum leptin levels and expression of both short ( ObRs ) and long ( ObRb ) form of leptin receptor in the hypothalamus , pituitary and placenta were measured in the course of pregnancy . ^^^ The expression of both short and long forms of the leptin receptor in the hypothalamus decreases in the course of pregnancy and increases after the delivery . ^^^ In the pituitary , however , a decrease of leptin receptor mRNA during pregnancy was observed only for ObRb . ^^^ Analysis of placental leptin receptor expression demonstrated an increase of ObRb and constant high levels of ObRs mRNA . ^^^ In addition , changes in ObR expression are suggestive for : 1 ) leptin resistance in the hypothalamus and pituitary ; and 2 ) an increased leptin dependent signaling in the placenta . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Polymorphisms in the leptin receptor ( LEPR ) putative association with obesity and T2DM . ^^^ Leptin controls energy balance and food intake through the leptin receptor in the hypothalamus of the brain , which suggests that some polymorphisms of the leptin receptor gene ( LEPR ) might contribute to obesity or obesity related diseases . ^^^
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However , the ubiquitous distribution of OB R leptin receptors in almost all tissues underlies the pleiotropism of leptin . ^^^
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METHODS : The presence of leptin receptor was examined by means of RT PCR and immunofluorescence analysis in freshly isolated blood eosinophils and tissue eosinophils . ^^^ The antiapoptotic effects of leptin were concentration dependent and blocked by an anti leptin receptor mAb . ^^^
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The role of the soluble leptin receptor ( sOB R ) and its regulation in children with protein energy malnutrition ( PEM ) is poorly understood . ^^^
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The long form of leptin receptor ( Ob R ( b ) ) is required for satiety ; mice lacking this receptor ( db / db mice ) are also substantially obese . ^^^ Leptin was increased in serum of db / db mice , and pulmonary mRNA expression of short form of leptin receptor ( Ob R ( a ) ) was similar in db / db and WT mice . ^^^ Differences between ob / ob mice , which lack leptin , and db / db mice , which lack Ob R ( b ) but not Ob R ( a ) , suggest leptin , acting through Ob R ( a ) , can modify some pulmonary responses to O ( 3 ) . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Recently , we identified in normally type 1 diabetes prone NOD / LtJ mice a spontaneous new leptin receptor ( LEPR ) mutation ( designated Lepr ( db 5J ) ) producing juvenile obesity , hyperglycemia , hyperinsulinemia , and hyperleptinemia . ^^^ In conclusion , metabolic disturbances elicited by a type 2 diabetes syndrome ( insulin and / or leptin resistance , but not hypercorticism ) appear to suppress type 1 diabetes development in NOD Lepr ( db 5J ) / Lt by inhibiting activation of T effector cells . . ^^^ Novel leptin receptor mutation in NOD / LtJ mice suppresses type 1 diabetes progression : 2 . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Changes in leptin , leptin receptor and fatty acids levels during chemoradiotherapy for oesophageal cancer ] . ^^^ METHODS AND RESULTS : In this study we examined the nutritional status ( pre treatment weight loss , actual weight , body mass index ) , serum levels of leptin , soluble leptin receptor , TNF alpha , IGF 1 and plasma phosphatidyl cholin fatty acids before the beginning of treatment , after the onset of treatment and shortly before its completion . ^^^
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Cardiomyocytes from ob / ob mice displayed reduced expression of the leptin receptor Ob R , larger cross sectional area , decreased peak shortening and maximal velocity of shortening / relengthening , and prolonged relengthening but not shortening duration compared with lean counterparts . ^^^
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Two experiments were conducted to evaluate the effects of dietary energy level and source of oil on leptin mRNA and long form leptin receptor ( Ob Rl ) mRNA expression in dorsal , abdominal and visceral adipose tissues in young growing pigs . ^^^
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Blockade of leptin with anti leptin Abs or with a soluble mouse leptin receptor chimera ( ObR : Fc ) , either before or after onset of EAE , improved clinical score , slowed disease progression , reduced disease relapses , inhibited PLP ( 139 151 ) specific T cell proliferation , and switched cytokine secretion toward a Th2 / regulatory profile . ^^^
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Here we show that leptin receptor immunolabeling can be detected in cultured cerebellar granule cells , being expressed at the somatic plasma membrane and also concentrated at synapses . ^^^
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The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes . ^^^
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Adipocytes express the leptin receptor ; therefore , it is realistic to expect a direct effect of leptin on adipocyte growth and metabolism . ^^^
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Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma . ^^^ AIM : To investigate the expression of leptin and leptin receptor ( ob R ) in intestinal type gastric cancer and precancerous lesions , and to explore the possible mechanism and role of the leptin system in developing intestinal type gastric adenocarcinoma . ^^^ METHODS : Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions , including intestinal metaplasia and mild to severe gastric epithelial dysplasia . ^^^ RESULTS : Dual expression of leptin and leptin receptor were detected in 80 % ( 16 / 20 ) intestinal metaplasia , 86 . 3 % ( 25 / 30 ) mild gastric epithelial dysplasia , 86 . 7 % ( 26 / 30 ) moderate gastric epithelial dysplasia , 93 . 3 % ( 28 / 30 ) severe gastric epithelial dysplasia , 91 . 3 % ( 55 / 60 ) intestinal type gastric adenocarcinoma and 30 . 0 % ( 9 / 30 ) diffuse type gastric carcinoma . ^^^ The percentage of dual expression of leptin and leptin receptor in intestinal type gastric adenocarcinoma was significantly higher than that in diffuse type gastric adenocarcinoma ( c 2 = 37 . 022 , P < 0 . 01 ) . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Up regulation of leptin receptor and activation of JAK 1 and 2 were not affected by DLPC+SAMe , whereas phosphorylation of ERK1 / 2 and p 38 was blocked by DLPC+SAMe or catalase , suggesting an H2O2 dependent mechanism . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Decreased soluble leptin receptor levels in women with polycystic ovary syndrome . ^^^ The soluble leptin receptor ( sOB R ) is the most important leptin binding protein , thus influencing the biologically active free leptin level . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In the hypothalamus , restorative gene therapy has been successfully implemented in Brattleboro rats , an arginine vasopressin ( AVP ) mutant which suffers from diabetes insipidus , in Koletsky ( fa ( k ) / fa ( k ) ) and in Zucker ( fa / fa ) rats which have leptin receptor mutations that render them obese , hyperphagic and hyperinsulinemic . ^^^ In the above models , viral vectors expressing AVP , leptin receptor b and proopiomelanocortin , respectively were stereotaxically injected in the relevant hypothalamic regions . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
We have at first identified the expression of Ob Rb and Ob Ra leptin receptor isoforms in MC3T3 E 1 and observed that these cells respond to mrleptin treatments . ^^^
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Ubiquitylation of leptin receptor OB Ra regulates its clathrin mediated endocytosis . ^^^ We propose that mono ubiquitin conjugates act as internalization motifs for clathrin dependent endocytosis of leptin receptor OB Ra . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In addition to glucose and insulin , we measured adiponectin , leptin , soluble leptin receptor ( the main leptin binding protein ) , and tumor necrosis factor alpha . ^^^ We found that birth weight was related to maternal height , baseline BW , and BW change , and also albeit less strongly to insulin , adiponectin , leptin , and soluble leptin receptor concentrations . ^^^
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Second , we performed double label in situ hybridisation for KiSS 1 mRNA and the leptin receptor ( Ob Rb ) mRNA and found that almost one half ( approximately 40 % ) of KiSS 1 mRNA expressing cells in the arcuate nucleus expressed Ob Rb mRNA . ^^^
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Leptin exerts its physiological action through its specific receptor ( LEPR ) . ^^^ CONCLUSION : Our results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress , supporting our hypothesis for leptin involvement in cancer pathogenesis . . ^^^ Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Rat thymectomy effects on leptin receptor and T bet : erythroid hyperplasia with maturation arrest and suppressed T cell mediated hepatotoxicity . ^^^ Polymerase chain reaction ( PCR ) of PB and MLN showed compensatory activated leptin receptor ( LR ) and T bet DNA in 19 Tx rats ( Exp A and B ) with abnormal FCM findings . ^^^
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In contrast , UCP 1 expression in Epi of leptin receptor mutant mice did not alter food intake , though it significantly decreased blood glucose and insulin levels . ^^^
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The leptin receptor belongs to the class 1 cytokine receptor superfamily and possesses strong homology to the signal transducing subunits of the IL 6 receptor . ^^^ We showed that experimental uremic cachexia was attenuated in db / db mice , a model of leptin receptor deficiency . ^^^
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In this study , we investigated the presence of leptin receptor in pancreatic islets and the effect of exogenous leptin administration in Podarcis sicula on glucose metabolism . ^^^ Our data show the presence of leptin receptor immunoreactivity in the endocrine pancreas suggesting that leptin may act at a peripheral level as previously postulated in mammals . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Increased expression of leptin and the leptin receptor as a marker of breast cancer progression : possible role of obesity related stimuli . ^^^ To evaluate whether the leptin system could become a target in breast cancer therapy , we examined the expression of leptin and its receptor ( ObR ) in primary and metastatic breast cancer and noncancer mammary epithelium . ^^^ We also studied whether the expression of leptin / ObR in breast cancer can be induced by obesity related stimuli , such as elevated levels of insulin , insulin like growth factor 1 ( IGF 1 ) , estradiol , or hypoxic conditions . ^^^ EXPERIMENTAL DESIGN : The expression of leptin and ObR was examined by immunohistochemistry in 148 primary breast cancers and 66 breast cancer metastases as well as in 90 benign mammary lesions . ^^^ The effects of insulin , IGF 1 , estradiol , and hypoxia on leptin and ObR mRNA expression were assessed by reverse transcription PCR in MCF 7 and MDA MB 231 breast cancer cell lines . ^^^
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Techniques : new pharmacological perspectives for the leptin receptor . ^^^ Both stimulation and inhibition of the molecular target of leptin , the leptin receptor ( LR ) , might find applications in disease treatment . ^^^
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The leptin induced growth cone spreading was hampered in cortical neurons from Lepr ( db / db ) mice lacking functional leptin receptors ; it was associated with localized Ser 9 GSK3beta phosphorylation and mimicked by the GSK3beta inhibitor SB 216763 . ^^^
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Differences with respect to single nucleotide polymorphisms in selected genes [ ie , estrogen receptor alpha ( XbaI and PvuII ) , estrogen receptor beta ( AluI ) , and estrogen receptor beta ( cx ) ( Tsp509I ) , endothelial nitric oxide synthase ( Glu298Asp ) , apolipoprotein E ( Apo E 2 , E 3 , and E 4 ) , cholesteryl ester transfer protein ( TaqIB ) , and leptin receptor ( Gln223Arg ) ] and with respect to equol production were investigated . ^^^
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Leptin receptor expression and cell signaling in breast cancer . ^^^ Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking . ^^^ The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells . ^^^ Multiplex RT PCR was performed to determine relative mRNA expression levels of the human short ( huOB Ra ) or long ( huOB Rb ) leptin receptor isoforms , or SOCS 3 . ^^^ The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS 3 mRNA expression . . ^^^
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Mapping of binding site 3 in the leptin receptor and modeling of a hexameric leptin . leptin receptor complex . ^^^ The leptin . leptin receptor ( LR ) system shows strong similarities to the long chain cytokine interleukin 6 ( IL 6 ) and granulocyte colony stimulating factor ( G CSF ) cytokine . cytokine receptor systems . ^^^
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Our data suggested that the introduction of HCV core protein results in an increase in expression of IL 6 , gp 130 , leptin receptor , and Stat 3 . ^^^
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We have investigated olfactory mediated pre ingestive behavior in leptin ( ob / ob ) and leptin receptor ( db / db ) mutant mice compared to age and gender matched wild type ( wt ) mice . ^^^
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To determine whether this may be caused by increased pregnancy leptin levels , leptin receptor ( Ob Rb ) mutant ( fa / fa ) and wild type ( FA / FA ) female Zucker rats and Sprague Dawley rats were fed during pregnancy an obesity inducing high fat diet ( OID ) that increased pregnancy weight gain , or a control diet . ^^^ Exposure to the OID during pregnancy increased 7 , 12 dimethylbenz [ a ] anthracene ( DMBA ) induced mammary tumorigenesis in all genetic backgrounds , including leptin receptor mutant Zucker rats . ^^^
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We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood , which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor . . ^^^
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We examined the genetic associations of the G 2548A polymorphism in the promoter of the leptin ( LEP ) gene and the Gln223Arg ( Q223R ) polymorphism of the leptin receptor ( LEPR ) gene with obesity . ^^^
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Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome : relationship to insulin resistance and androgens . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Here we show that peripheral leptin administration induces the expression of phospho signal transducer and activator of transcription 3 immunoreactivity ( pSTAT 3 IR ) , a marker of leptin receptor signaling , in more than 50 % of NTS POMC EGFP neurons . ^^^
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Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs . ^^^ Therefore , in the present study , an expression of genes coding for leptin and long form leptin receptor ( Ob Rb ) was determined by a semiquantitative reverse transcription polymerase chain reaction ( RT PCR ) in the discrete areas of porcine hypothalamus ( medial basal hypothalamus MBH , preoptic area POA , stalk median eminence SME ) and pituitary ( anterior AP and posterior / neural NP parts ) during the luteal phase of the cycle ( days 10 12 and 14 16 ) and two early stages of pregnancy ( days 14 16 and 30 32 ) . ^^^
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Transcripts corresponding to the short leptin receptor form were present in mammary tissue , but those corresponding to the long signaling form were not detected in either mammary tissue or cells . ^^^
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The plasma soluble leptin receptor concentrations changed in the opposite direction , leading to an increase in the free leptin index , including in the three patients whose tumor was reduced without surgery . ^^^ CONCLUSIONS : The obesity that occurs after treatment of hypothalamic tumors is not due to dysregulation of leptin secretion because it and plasma soluble leptin receptor remain regulated by factors like testosterone . ^^^
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Hepatic insulin resistance in the leptin receptor defective Zucker fa / fa rat is associated with impaired glycogen synthesis and increased activity of phosphorylase a . ^^^ Diminished hepatic R 6 expression in the leptin receptor defective fa / fa rat may be a contributing factor to the elevated phosphorylase activity and / or its high control strength on glycogen synthesis . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Leptin induces TGF beta synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell . ^^^ The present study was designed to determine whether functional leptin receptor is expressed by human peritoneal mesothelial cells and if so , the possible implication in dialysis . ^^^ Both mRNA and protein of the full length leptin receptor are constitutively expressed in mesothelial cells . ^^^ The leptin receptor expression in mesothelial cells was upregulated by glucose but not leptin . ^^^ The TGF beta synthesis induced by leptin was amplified by glucose through increased leptin receptor expression . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In this study , we investigated the effect of leptin on the fetal cingulate cortex , since the leptin receptor is expressed in the neurons of the cingulate cortex , which is involved in emotion as well as in sensory , motor , and cognitive processes . ^^^
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The expression of hypothalamic P2Y1 receptor / nNOS mRNA and protein and of leptin receptor mRNA were enhanced after restricted feeding . ^^^
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This study assesses the contribution in elderly men of leptin and the Gln223Arg leptin receptor gene ( LEPR ) polymorphism to the variation in bone homeostasis , in relation to body composition and free estradiol as major confounders . ^^^ METHODS : Serum leptin , LEPR genotype , baseline bone mineral density ( BMD ) , longitudinal BMD changes at the hip and forearm , and biochemical markers of bone turnover were determined . ^^^ LEPR genotypes and serum leptin were not associated . ^^^ Serum bone specific alkaline phosphatase ( S BAP ) was associated with LEPR genotypes ( P = 0 . 05 ) and urinary C terminal telopeptides of type 1 collagen ( U CTX ) were associated with leptin levels ( P = 0 . 03 ) , independently from age , fat mass and free estradiol . ^^^ Baseline BMD at the hip and forearm was neither associated with leptin nor with LEPR genotypes . ^^^
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The tumors in this group expressed higher levels of leptin receptor and activated Akt , and contained fewer apoptotic cells than those in the controls . ^^^ Our results indicate that high birth weight is related to shortened latency to develop mammary tumors perhaps reflecting an increase in activated MAPK levels and increased tumor growth perhaps caused by a lower apoptotic response due to higher leptin receptor and activated Akt levels in the tumors . . ^^^
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Leptin concentrations increased from 23 . 0 + / 17 . 1 ng / mL to 40 . 9 + / 27 . 2 ng / mL ( p = . 018 ) , whereas the soluble leptin receptor concentrations remained stable during mirtazapine treatment . ^^^
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All fat depots were dissected and weighed , and expression of the appetite regulating neuropeptides and the leptin receptor ( OBRb ) were determined by in situ hybridization . ^^^
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Considering that the PMV CART neurons also express the leptin receptor , as well as the fact that they project to areas related to reproduction , we hypothesize that PMV CART neurons integrate nutritional and environmental ( olfactory ) information , being apt to modulate male reproductive behavior . . ^^^
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Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation . ^^^ We have tested monoclonal antibodies ( mAbs ) to the human leptin receptor ( ObR ) for antagonist activity using a leptin signalling bioassay . ^^^ In conclusion , this study has identified a mAb to the human leptin receptor which inhibits leptin signalling and acts as a leptin antagonist in vitro . . ^^^ The 9F8 mAb displaced leptin binding to human ObR and enzymatically generated Fab fragments of 9F8 retained antagonist activity . ^^^ Purified 9F8 rFab bound to human ObR and exhibited leptin antagonist activity . ^^^
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We confirmed the known interactions of suppressor of cytokine signalling 3 ( SOCS 3 ) and STAT 5 with the Y 985 and Y 1077 motifs of the leptin receptor , respectively . ^^^
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Phosphorylation of Jak 2 on Ser ( 523 ) inhibits Jak 2 dependent leptin receptor signaling . ^^^ The leptin receptor , LRb , and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling . ^^^
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In conclusion , these results suggest that swim training induced transcriptional activation of hepatic PPARalpha target enzymes and UCP 2 may effectively prevent body weight gain , adiposity , and lipid disorders caused by leptin receptor deficiency in both sexes of mice . . ^^^
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CONCLUSION : These data suggest a direct role for PAI 1 in renal matrix expansion and metabolic control in diabetes , but they also highlight important adverse outcomes that include male runting and premature death in mice with diabetes due to an inactive leptin receptor . . ^^^
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Sixteen women patients with anorexia nervosa and thirteen healthy women of comparable age were examined clinically and blood samples were taken for estimation of serum levels of ghrelin , leptin , soluble leptin receptor , IGF 1 , IGFBP 1 and IGFBP 3 . ^^^
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Leptin receptor expression and signaling in lymphocytes : kinetics during lymphocyte activation , role in lymphocyte survival , and response to high fat diet in mice . ^^^ We report in this study that leptin receptor ( ObR ) is expressed on resting normal mouse CD 4 ( + ) , CD 8 ( + ) , B cells , and monocyte / macrophages . ^^^ Leptin binding to ObR results in increased STAT 3 activation in T cells , with a different activation pattern in resting vs anti CD 3 Ab stimulated T cells . ^^^ B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin , and they show higher surface expression of ObR , compared with T cells . ^^^ Furthermore , ObR / STAT 3 mediated signaling in T lymphocytes is decreased in the diet induced obese mouse model of obesity and leptin resistance . ^^^
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In this study , we observed significantly increased plasma leptin levels combined with decreased soluble leptin receptor ( sOB R ) levels in 18 chronic ITP patients compared with 14 controls . ^^^ We also demonstrated significantly elevated mRNA expression of long form leptin receptor ( Ob Rb ) on peripheral blood mononuclear cells ( PBMCs ) from chronic ITP patients . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Results from multiple studies demonstrate that ( 1 ) chronically elevated central leptin decreases hypothalamic leptin receptor expression and protein levels and impairs leptin signaling ; ( 2 ) leptin resistance and obesity are associated with reduced leptin receptors and diminished maximal leptin signaling capacity ; and ( 3 ) leptin resistance confers increased susceptibility to diet induced obesity . ^^^
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In this article , we report the identification and functional characterization of leptin and leptin receptor ( LR ) in Xenopus . ^^^
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Leptin and leptin receptor gene expression has been studied in placentas obtained from pre eclamptic patients , but not in those with chronic high blood pressure ( CHBP ) . ^^^
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Among these genes , LEP , which codifies leptin , and the LEPR gene encoding its receptor were extensively studied for variants that could explain the obese phenotype . ^^^ Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects . ^^^
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Phenotypic variation in constitutional delay of growth and puberty : relationship to specific leptin and leptin receptor gene polymorphisms . ^^^ Possible candidates are the leptin ( L ) and the leptin receptor ( LR ) genes , as the leptin axis links nutritional status to pubertal development . ^^^
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RESULTS : There was a strong association with significantly elevated serum leptin levels , high body mass index , and higher frequency of LEPR longer alleles in patients with prostate cancer than in control subjects . ^^^ Analysis within groups 1 ( low leptin level and low body mass index ) and 2 ( other ) showed a significant association only in group 2 , with high frequency of OB gene variants ( LEPR long alleles and LEP short alleles ) in patients with prostate cancer but not in control subjects . ^^^
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Moreover , both angiotensin 2 and ET 1 increased the gene expression of the short form ( OBRa ) by 180 % and long form ( OBRb ) of leptin receptors by 200 % , and this increase was abolished by both leptin receptor and leptin antibodies and leptin triple mutant . ^^^
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Obesity related leptin receptor polymorphisms and gallstones disease . ^^^ OBJECTIVE : Investigate the association between polymorphisms in the leptin receptor gene associated with obesity and gallstone disease . ^^^ Genomic DNA was isolated from lymphoblastoid cells , and Q223R and K656N polymorphisms in the leptin receptor gene were typed using polymerase chain reaction . ^^^ CONCLUSION : Obesity related leptin receptor polymorphisms are not associated with gallstones disease . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
In the hypothalamus , restorative gene therapy has been successfully implemented in Brattleboro rats , an arginine vasopressin ( AVP ) mutant which suffers from diabetes insipidus , and in Koletsky ( fa ( k ) / fa ( k ) ) and in Zucker ( fa / fa ) rats which have leptin receptor mutations that render them obese , hyperphagic and hyperinsulinemic . ^^^ In the above models , viral vectors expressing AVP , leptin receptor b and proopiomelanocortin , respectively , were stereotaxically injected in the relevant hypothalamic regions . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Lifelong obliteration of STAT 3 signaling via the leptin receptor in mice ( s / s mice ) results in severe hepatic insulin resistance that is comparable to that observed in db / db mice , devoid of leptin receptor signaling . ^^^
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The db / db mouse develops features of type 2 diabetes mellitus as the result of impaired signaling through its abnormal leptin receptor . ^^^
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Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure . ^^^ The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels . ^^^ The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme linked immunoassay and radioimmunoassay , respectively . ^^^ RESULTS : Mean plasma leptin levels were significantly higher , whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group ( 10+ / 4 . 8 5 6+ / 2 . 7 ng / mL , P < . 001 and 18+ / 7 5 27+ / 9 IU / mL , P < . 001 , respectively ) . ^^^
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Leptin gene and leptin receptor gene ] . ^^^
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Even considering that norms have not yet been proposed for pharmacological interventions with leptin for use directly on humans , in our work we have studied by immunohistochemistry methods the distribution of leptin and its receptor ( Ob R ) in the ovaries of the female dog as a biological model , in the pre and postpubertal phases and in other phases of the ovarian cycle . ^^^
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Pregnant Sprague Dawley rats ( n = 12 ) at D 14 , D 16 and D 18 were sacrificed and fetal whole brain and placenta removed and examined for mRNA levels of orexigenic ( neuropeptide Y ( NPY ) , agouti related peptide ( AgRP ) ) and anorexigenic ( cocaine and amphetamine regulated transcript ( CART ) , pro opiomelanocortin ( POMC ) ) peptides and leptin receptor ( OB Rb ) using real time reverse transcription polymerase chain reactions ( RT PCR ) . ^^^
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Obesity is a state of leptin resistance in which the membrane leptin receptor and the JAK STAT pathway are blocked . ^^^
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Distinct impaired regulation of SOCS 3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women . ^^^ Animal studies have illustrated the importance of the expression in adipose tissue of the leptin receptor ( OB R ) , and of SOCS 3 an inhibitor of the leptin signaling pathway , in body weight regulation . ^^^
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Furthermore , leptin deficient ( ob / ob ) and leptin receptor deficient ( db / db ) mice did not show slower weight gain on the KD . ^^^
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MATERIALS AND METHODS : Associations between preoperative serum leptin levels and leptin receptor expression in tumor specimens and various clinicopathological parameters were analyzed in 57 patients with renal cell carcinoma . ^^^ Of 57 tumors 22 ( 38 . 6 % ) demonstrated high leptin receptor expression . ^^^ Serum leptin levels were significantly higher in patients with vs without tumor specimen venous invasion ( p = 0 . 030 ) and higher in patients with high vs low leptin receptor expression ( p = 0 . 019 ) . ^^^ There were significant associations between high leptin receptor expression and the presence of venous invasion ( p = 0 . 013 ) , histological type ( p = 0 . 0076 ) and regional lymph node metastasis ( p = 0 . 047 ) . ^^^ CONCLUSIONS : Leptin and leptin receptor could have a key role in the invasion of renal cell carcinoma and they could be valuable predictors of progression . . ^^^
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MATERIALS AND METHODS : Leptin receptor expression in the 6 human renal cancer cell lines Caki 1 , ACHN , 769P , A 498 , SKRC 44 and SKRC 49 , and in the murine renal cancer cell line Renca was examined by reverse transcriptase polymerase chain reaction and Western blotting . ^^^ RESULTS : Leptin receptor was detected in all renal cancer cells examined at the mRNA and protein levels . ^^^
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In GK rats , leptin induced phosphorylation of signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus ( ARC ) , but not of the ventromedial hypothalamus , whereas the mRNA level of functional leptin receptor was unaltered . ^^^
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Indirect effects of leptin receptor deficiency on lymphocyte populations and immune response in db / db mice . ^^^ Leptin deficient ob / ob and leptin receptor ( Ob rb ) deficient db / db mice display a marked thymic atrophy and exhibit defective immune responses . ^^^ To study the relative contributions of direct and indirect effects of leptin on the immune system in a normal environment , we generated bone marrow chimeras ( BMCs ) by transplantation of leptin receptor deficient db / db , or control db / + , bone marrow cells into wild type ( WT ) recipients . ^^^ Conversely , thymus weight and cell number were decreased in the reverse graft setting in WT to db / db BMCs , indicating that expression of the leptin receptor in the environment is important for T cell development . ^^^ In contrast , leptin receptor deficiency affects the immune system indirectly via changes in the systemic environment . . ^^^
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Animal models demonstrate that leptin is required for control of bodyweight and reproduction , since mice defective in leptin or the leptin receptor are obese , hyperphagic insulin resistant and infertile . ^^^
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The kidney expresses abundant concentrations of the small isoform of the leptin receptor ( Ob Ra ) . ^^^
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CONCLUSIONS : Patients with Asn 656 allele of LEPR gene have a different response than wild type patients , and Lys656Lys patients have a significant decrease in weight , BMI , fat mass , waist circumference , systolic blood pressure and leptin levels . . ^^^ Leptin receptor Lys656Asn polymorphism is associated with decreased leptin response and weight loss secondary to a lifestyle modification in obese patients . ^^^ The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on leptin response and weight loss secondary to a lifestyle modification ( Mediterranean hypocaloric diet and exercise ) in obese patients . ^^^
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While leptin receptor ( Lepr ) function has been well studied in the hypothalamus , the functional relevance of Lepr expression in the ventral tegmental area ( VTA ) has not been investigated . ^^^ Here , we show that VTA dopamine neurons express Lepr mRNA and respond to leptin with activation of an intracellular JAK STAT pathway and a reduction in firing rate . ^^^ Direct administration of leptin to the VTA caused decreased food intake while long term RNAi mediated knockdown of Lepr in the VTA led to increased food intake , locomotor activity , and sensitivity to highly palatable food . ^^^ Leptin receptor signaling in midbrain dopamine neurons regulates feeding . ^^^
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Zucker rats , which naturally develop leptin receptor mutations , and their lean littermate rats were fed a choline deficient , amino acid defined diet . ^^^
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Expression pattern of leptin and leptin receptor ( OB R ) in human gastric cancer . ^^^ AIM : To examine the expression of leptin and its receptor , OB R , in normal gastric mucosa and neoplasia . ^^^ METHODS : By immunohistochemical staining using specific antibodies , we evaluated the expression of leptin and OB R in 207 gastric carcinomas ( 100 early and 107 advanced carcinomas ) and analyzed their relationship with clinicopathological features . ^^^ The expression of OB R showed a significant correlation with the level of leptin expression . ^^^ The expression levels of both leptin and OB R tended to increase as the depth of tumor invasion or TMN stage increased ( P < 0 . 01 ) . ^^^
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Gh and IGF 1 increase leptin receptor expression in prepubertal pig ovaries : the role of leptin in steroid secretion and cell apoptosis . ^^^ The expression of the functional long form leptin receptor ( Ob Rb ) mRNA was examined by semi quantitative reverse transcription polymerase chain reaction ( RT PCR ) in follicular cells cultured with GH or IGF 1 . ^^^ Both GH and IGF 1 increased leptin receptor expression in prepubertal pig ovaries . ^^^ In conclusion , we infer that ( 1 ) leptin directly affects ovarian function in prepubertal animals by its action on oestradiol secretion and cell apoptosis , ( 2 ) GH and IGF 1 modulate the action of leptin , and ( 3 ) at least in part , the direct effect of GH / IGF 1 on leptin production is due to an action on leptin receptor expression . . ^^^
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Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes ( FVB Lepr ( db ) ) and obese ( DBA Lep ( ob ) ) mice . ^^^ This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr ( db ) mutation to the FVB / NJ strain and the Lep ( ob ) mutation to the DBA / 2J strain . ^^^
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These data suggest that both the db gene and the hypothalamus are downstream of the ob gene in the pathway that regulates adipose tissue mass and are consistent with previous experiments suggesting that the db locus encodes the ob receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
As part of an effort to identify informative molecular markers for genetic analysis of human pedigrees segregating for obesity , we have developed a genetic map of human 1p in the region of the OB receptor ( OBR ) , the gene that is defective in murine diabetes ( Obrdb ) and rat Zucker fatty ( Obrfa ) mutations located on mid chromosome 4 and chromosome 5 , respectively . ^^^ Mapping of the OB receptor to 1p in a region of nonconserved gene order from mouse and rat to human . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The expression of short from of leptin receptor gene during early pregnancy in the pig examined by quantitative real time RT PCR . ^^^ The study was conducted to determine gene expression of short form of leptin receptor ( OB Rs ) using real time RT PCR in distinct tissues of the central nervous system ( medial basal hypothalamus , preoptic area , stalk median eminence ) , pituitary and reproductive tract ( corpus luteum , ovarian stroma , endometrium , myometrium , and trophoblast ) in pigs during luteal phase of the cycle and early gestation . ^^^ Summarizing , the expression of the short form of leptin receptor mRNA was found in majority of tested tissues including hypothalamus , pituitary and reproductive tract and their levels fluctuated depending on the phase ( mid and late luteal ) of the cycle and the day of pregnancy ( early and late stage of implantation ) . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Nesfatin 1 induced anorexia occurs in Zucker rats with a leptin receptor mutation , and an anti nesfatin 1 antibody does not block leptin induced anorexia . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes ( Lepr ( db ) ) or obese ( Lep ( ob ) ) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism , sensitivity of diabetic males to exogenous insulin , and a milder and male biased diabetes syndrome that is not associated with widespread beta cell necrosis and islet atrophy , and that often remits with age . . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
It acts through its receptor ( OB R ) , which is a product of db gene . ob and OB R in conjunction with neuropeptide Y , melanocyte stimulating hormone and melanocortin 4 receptor have been found to control adiposity . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism ( StAR , CYP 11 , CYP 17 , CYP 19 HSD17B1 3 , HSD3B1 2 ) , gonadotropin and gonadal hormones action ( ACTR 1 , ACTR2A B , FS , INHA , INHBA B , INHC , SHBG , LHCGR , FSHR , MADH 4 , AR ) , obesity and energy regulation ( MC4R , OB , OBR , POMC , UCP 2 3 ) , insulin secretion and action ( IGF 1 , IGF1R , IGFBPI 1 3 , INS VNTR , IR , INSL , IRS 1 2 , PPARG ) and many others . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The expression cloning of a central receptor , OB R , from the mouse choroid plexus soon followed . ^^^ The OB R receptor was found to be expressed in the choroid plexus , the hypothalamus as well as several peripheral tissues . ^^^ OB R exists in multiple forms ; the two major forms are a short form ( with a truncated intracellular domain ) and long form ( with the complete intracellular domain ) . ^^^ Initial in situ hybridization studies have demonstrated the mRNA for the long form OB R receptor to be localized to the hypothalamus as well as peripheral sites . ^^^ Recently , it was demonstrated that the db gene encodes the OB R receptor . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Mutations in the obese gene ( OB ) or in the gene encoding the OB receptor ( OB R ) result in obesity , infertility and diabetes in a variety of mouse phenotypes . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
To exert such effects , it may function as an endogenous ligand in the CNS , since specific receptors ( OB R ) have been recently reported to be widely distributed in the brain . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
Here we show in mice that both the long and short form of the OB receptor are expressed not only in the hypothalamus but also in the amygdala and pituitary . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
The fa / fa genotype was determined from the size of the product after Msp 1 digestion of the Ob receptor gene obtained by polymerase chain reaction amplification of genomic DNA . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
At least six alternatively spliced forms of the OB receptor ( OB R ) gene have been described , all of which encode proteins containing the OB R extracellular domain . ^^^ One splice variant encodes a receptor with a long intracellular domain , OB RL , that has been implicated in OB R signaling . ^^^ Here , we have used in situ hybridization to examine the localization of OB R splice variants in brain and peripheral tissues of adult and newborn mice . ^^^ Using a probe hybridizing with all known splice variants , we confirmed that OB R mRNA was widely distributed in the adult tissues . ^^^ We now demonstrate that OB R mRNA is expressed in peripheral tissues ; primarily associated with connective tissues . ^^^
Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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Interacting proteins: P41159 and P48357 Pubmed SVM Score :0.0
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