Affinage

LEPR

Leptin receptor · UniProt P48357

Length
1165 aa
Mass
132.5 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LEPR (OB-R) is a single membrane-spanning class I cytokine receptor, structurally related to gp130 and the G-CSF/LIF receptors, that serves as the principal signal-transducing receptor for leptin and thereby links peripheral energy stores to central control of food intake and metabolism (PMID:8548812). A single extracellular residue (Gln269) is critical for high-affinity leptin binding, and its loss in the rat fatty (fa) allele abolishes surface binding and produces obesity, establishing LEPR loss-of-function as causal for the obese phenotype (PMID:8690163). LEPR signals as a spontaneously formed homo-oligomer—aggregation of two intracellular domains is sufficient for activation, and signaling proceeds without recruitment of gp130 or LIFR (PMID:9020115, PMID:9038364). The long isoform (Ob-Rb) activates STAT1/3/5, ERK/MAPK, and, through its intracellular tyrosine residues (Tyr985, Tyr1077, Tyr1138), the PI3K/AKT/mTOR axis, whereas truncated short isoforms expressed in db/db animals fail to activate STAT3 (PMID:9020115, PMID:9003804, PMID:30145913). Functional isoforms are anatomically segregated in the brain, with Ob-Rb concentrated in hindbrain neuronal nuclei and short variants in choroid plexus and leptomeninges (PMID:9421394). In the brain, leptin acts through distinct LepRb neuron populations: GABAergic dorsomedial hypothalamic neurons co-expressing Glp1r suppress food intake and body weight and mediate the efficacy of GLP-1R/LepR dual agonists (PMID:37581939, PMID:39630884), while a lateral hypothalamic GABAergic LEPR population drives appetitive reward behaviors via projections to the VTA (PMID:34433027). LepR additionally governs leptin entry into the brain: tanycytic transcytosis requires sequential activation of a LepR-EGFR complex, and its loss blocks leptin entry and produces hyperphagia, lipogenesis, and glucose intolerance (PMID:34341568), while LepR in brain barrier endothelial/epithelial cells controls food reward distinct from homeostatic feeding (PMID:29254602). LepR+ pancreatic cells, where LepR co-localizes with GIPR, mediate the glycemic but not the anorectic actions of incretin co-agonism (PMID:38492844). Beyond CNS and metabolic roles, LepR transcription is induced by HIF-1α via a promoter HRE in cancer cells (PMID:25130171), and leptin/OB-R signaling promotes M1 macrophage polarization through JNK/STAT3/AKT, linking it to obesity-related inflammation (PMID:37488474).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Established the molecular identity of the leptin receptor, answering what cell-surface protein transduces the leptin signal and placing it in the class I cytokine receptor family.

    Evidence expression cloning from mouse choroid plexus with a leptin-AP fusion probe and [125I]leptin binding

    PMID:8548812

    Open questions at the time
    • Did not resolve which isoform mediates intracellular signaling
    • Binding stoichiometry and oligomeric state not addressed
  2. 1996 High

    Connected receptor function to phenotype by showing a single extracellular residue governs leptin binding and that its loss causes obesity.

    Evidence introduction of the rat fa Gln269Pro mutation into Lepr cDNA, cell-surface binding assays, and co-segregation across 1028 meioses

    PMID:8690163

    Open questions at the time
    • Did not define the full leptin-binding interface
    • Downstream signaling consequences of binding loss not measured here
  3. 1997 High

    Defined the signaling logic of LEPR: it homo-oligomerizes independently of gp130/LIFR and uses two distinct intracellular regions to activate STATs and ERK, with the long domain required for STAT3.

    Evidence deletion/tyrosine-substitution mutagenesis, G-CSFR/OB-R chimeras, reciprocal Co-IP of tagged receptors, and STAT/ERK readouts across three studies

    PMID:9003804 PMID:9020115 PMID:9038364

    Open questions at the time
    • Did not map individual tyrosine residues to specific outputs in vivo
    • JAK kinase identity and recruitment not resolved in these studies
  4. 1998 Medium

    Showed that long and short LEPR isoforms are anatomically segregated in the brain, implying region-specific signaling versus transport roles.

    Evidence isoform-specific in situ hybridization in mouse and rat hindbrain

    PMID:9421394

    Open questions at the time
    • Expression mapping does not establish functional roles per region
    • Single-lab localization without functional perturbation
  5. 2001 Medium

    Demonstrated that LEPR-dependent feedback on leptin production is CNS-routed via the sympathetic nervous system in brown but not white fat, framing LEPR within a closed-loop energy-balance circuit.

    Evidence fa-allele segregation in rat pups, thermoneutral artificial rearing, norepinephrine administration, and Lep mRNA quantification

    PMID:11160998

    Open questions at the time
    • WAT regulatory mechanism left undefined
    • Indirect inference of SNS activity from metabolic rate
  6. 2016 Medium

    Dissociated leptin transport from OB-R signaling at the human BBB, showing OB-R signaling is dispensable for transcytosis and implicating LRP-2/megalin instead.

    Evidence human hCMEC/D3 BBB model with OB-R-neutralizing antibody, STAT3 phosphorylation, and transcytosis assays

    PMID:27037668

    Open questions at the time
    • Did not directly prove LRP-2 mediates transport
    • In vitro human model may differ from rodent barrier biology
  7. 2014 Medium

    Identified a transcriptional input to LEPR by showing HIF-1α directly drives Ob-R promoter activity in cancer cells.

    Evidence HIF-1α overexpression/knockdown, ChIP at the -828/-832 HRE, and xenograft models

    PMID:25130171

    Open questions at the time
    • Functional consequence of HIF-driven LEPR in tumor biology not fully defined
    • Single-lab finding restricted to pancreatic cancer cells
  8. 2017 High

    Showed brain-barrier LepR controls leptin transport governing food reward, separating this function from homeostatic feeding control.

    Evidence endothelial/epithelial-specific LepR knockout, brain leptin uptake perfusion, and high-fat-diet behavioral testing

    PMID:29254602

    Open questions at the time
    • Molecular transport machinery downstream of LepR not defined
    • Reward circuitry linkage inferred behaviorally
  9. 2021 High

    Defined tanycytic LepR as a leptin-responsive, transport-gating receptor requiring a sequential LepR-EGFR complex, controlling both brain leptin entry and systemic glucose handling.

    Evidence multiple tanycyte-specific LepR deletion models, Ca2+ imaging, phosphorylation assays, transport measurement, and metabolic/insulin-secretion phenotyping

    PMID:34341568

    Open questions at the time
    • Precise molecular coupling between LepR and EGFR not structurally resolved
    • Relationship to barrier-cell transport pathway not reconciled
  10. 2021 High

    Resolved hypothalamic LepRb circuitry into functionally distinct GABAergic populations: Glp1r-co-expressing neurons suppress feeding, while lateral hypothalamic LEPR neurons drive appetitive reward.

    Evidence single-nucleus RNA-seq, cell-type-specific ablation/reactivation, optogenetics, chemogenetics, and behavioral paradigms across two studies

    PMID:34433027 PMID:37581939

    Open questions at the time
    • Intracellular signaling distinguishing these populations not defined
    • Connectivity between feeding and reward LepR populations unresolved
  11. 2018 Medium

    Assigned a reproductive function to LEPR tyrosine signaling, showing the three intracellular tyrosines normally restrain the PI3K/mTOR pathway in ovarian follicles.

    Evidence Y123F (Tyr985/1077/1138-to-Phe) knock-in mice with follicle counting and pathway western blotting

    PMID:30145913

    Open questions at the time
    • Cannot attribute the phenotype to a single tyrosine residue
    • Cell-autonomous versus systemic contribution to infertility not separated
  12. 2023 Medium

    Extended LEPR function to immunity, showing leptin/OB-R signaling drives M1 macrophage polarization and neutrophil recruitment in obesity-related airway inflammation.

    Evidence db/db obR-deficient mice, pharmacological obR blockade, and BMDM in vitro signaling/cytokine assays

    PMID:37488474

    Open questions at the time
    • Direct versus systemic effects of obR loss not fully separated
    • Single-lab finding within a specific inflammation context
  13. 2024 High

    Pinpointed the tissue sites of incretin co-agonist action relative to LepR: DMH GABAergic LepRGlp1r neurons mediate anorexia, while LepR+ pancreatic cells expressing GIPR mediate the glycemic benefit.

    Evidence conditional Lepr/Gipr knockouts and Glp1r reactivation, scRNA-seq co-expression, dual-agonist pharmacology, and NHP immunohistochemistry across two studies

    PMID:38492844 PMID:39630884

    Open questions at the time
    • Signaling crosstalk between LepR and GIPR/GLP-1R in the same cells not defined
    • Pancreatic LepR's own ligand-dependent role not isolated from GIPR effects

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LEPR signaling outputs are differentially wired across the distinct neuronal, glial, barrier, pancreatic, and immune cell types to produce tissue-specific physiology remains unresolved.
  • No structural model of the ligand-bound oligomeric receptor in the corpus
  • Mechanism coupling LepR to EGFR and to incretin receptors not defined
  • How identical intracellular tyrosines yield divergent outcomes across tissues is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2
Partners
ANXA7EGFRGIPRLEP
Complex memberships
LEPR homo-oligomerLepR-EGFR complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LEPR (OB-R) was identified as a leptin-binding receptor by expression cloning from mouse choroid plexus using a leptin-alkaline phosphatase fusion protein as a probe. OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. cDNA expression library screening with leptin-AP fusion protein; ligand binding assay with [125I]leptin; sequence homology analysis Cell High 8548812
1996 A point mutation in the rat fatty (fa) allele of Lepr (Gln269Pro substitution caused by A→C nucleotide change at position 880) greatly reduces leptin binding at the cell surface, establishing that this single residue in the extracellular domain is critical for leptin binding and that loss of Lepr function causes the obese phenotype. PCR-based mutagenesis to introduce fa mutation into mouse Lepr cDNA; transient transfection; cell-surface leptin binding assay; genetic co-segregation analysis in 1028 meioses Diabetes High 8690163
1997 The long form of OB-R mediates ligand-induced activation of STAT1, STAT3, and STAT5 and stimulates transcription via IL-6 and hematopoietin receptor responsive gene elements. Deletion and tyrosine substitution mutagenesis identified two distinct regions of the intracellular domain required for signaling. Chimeric receptor experiments showed that aggregation of two OB-R intracellular domains is sufficient for ligand-induced activation, providing evidence for receptor homo-oligomerization. Cytoplasmic domain deletion and tyrosine substitution mutagenesis; G-CSF receptor/OB-R chimera signaling assays; STAT activation reporter assays; dominant negative repression experiments The Journal of biological chemistry High 9020115
1997 OB-R undergoes spontaneous homo-oligomerization (demonstrated by co-immunoprecipitation of two differently epitope-tagged OB-R molecules), and leptin signaling does not require interaction with gp130 or LIFR, as leptin stimulation does not induce tyrosine phosphorylation of gp130 or LIFR. Co-immunoprecipitation of differentially epitope-tagged OB-R constructs; tyrosine phosphorylation assays; Ba/F3 cell transfection and proliferation assay FEBS letters High 9038364
1997 Stimulation of the long form of OB-R leads to STAT3 tyrosine phosphorylation and p42ERK2 activation, but unlike gp130, OB-R long form does not induce tyrosine phosphorylation of the SHP-2 phosphatase. The truncated short form of OB-R expressed in db/db mice fails to activate STAT3, establishing that the long intracellular domain is required for STAT3 signaling. Tyrosine phosphorylation assays; STAT3 immunoprecipitation; ERK activation assays; comparison of long vs. truncated OB-R isoforms FEBS letters High 9003804
1998 The long splice variant of the leptin receptor (Ob-Rb) is expressed in hindbrain neuronal regions including the nucleus of the solitary tract, lateral parabrachial nucleus, and medullary reticular nucleus, while short receptor splice variants are abundantly expressed in leptomeninges and choroid plexus, establishing anatomical segregation of functional isoforms in the rodent brain. In situ hybridization with isoform-specific probes in mouse and rat hindbrain Endocrinology Medium 9421394
2001 LEPR-mediated feedback regulation of leptin (Lep) mRNA expression in brown adipose tissue (BAT) operates primarily through CNS-mediated effects on sympathetic nervous system (SNS) activity, whereas leptin expression in white adipose tissue (WAT) is regulated through mechanisms not directly dependent on SNS activity. Metabolic rate (SNS surrogate) explained 87% of variation in BAT-Lep mRNA. Genetic segregation of Lepr(fa) allele in rat pups; artificial rearing under thermoneutral conditions; oral norepinephrine administration; quantitative Lep mRNA measurement in BAT and WAT; plasma leptin measurement Physiological genomics Medium 11160998
2014 HIF-1α directly activates leptin receptor (Ob-R) transcription by binding to a hypoxia-responsive element (HRE) at -828/-832 in the Ob-R gene promoter in pancreatic cancer cells. HIF-1α silencing reduces Ob-R expression both in vitro and in xenograft models. HIF-1α overexpression and siRNA knockdown; chromatin immunoprecipitation (ChIP) for HRE binding; xenograft mouse models with HIF-1α inhibition; immunohistochemistry Cancer letters Medium 25130171
2017 LepR-mediated transport of leptin across brain barriers (endothelial and choroid plexus epithelial cells) controls food reward but is not required for homeostatic feeding control. Selective deletion of LepR in brain endothelial and epithelial cells caused hyperphagia and increased sensitivity to food reward on high-fat diet, while leaving median eminence and tanycyte LepR expression intact. Conditional LepR knockout in brain endothelial/epithelial cells (LepRbeKO mice); perfusion studies measuring brain leptin uptake; behavioral testing on high-fat diet; body weight and food intake measurements Molecular metabolism High 29254602
2021 Hypothalamic tanycytes express functional LepR that responds to leptin by triggering Ca2+ waves and target protein phosphorylation. Tanycytic transcytotic transport of leptin into the brain requires activation of a LepR-EGFR complex by leptin and EGF sequentially. Selective deletion of LepR in tanycytes blocks leptin entry into the brain, causing increased food intake, lipogenesis, and glucose intolerance through attenuated insulin secretion by pancreatic β-cells. Multiple complementary mouse models with selective LepR deletion in tanycytes; Ca2+ imaging; protein phosphorylation assays; leptin transport measurement; metabolic phenotyping; insulin secretion assays Nature metabolism High 34341568
2021 A GABAergic population of hypothalamic LepRb neurons co-expressing Glp1r (LepRbGlp1r neurons) plays a crucial role in suppression of food intake by leptin. Ablating Lepr from LepRbGlp1r neurons provoked hyperphagic obesity without impairing energy expenditure. Restoration of Lepr in GABAergic neurons required Lepr expression in Glp1r-expressing neurons to improve energy balance. Single-nucleus RNA-seq of enriched hypothalamic LepRb cells; cell-type-specific Lepr ablation; Lepr reactivation in otherwise Lepr-null mice; body weight and food intake measurements The Journal of clinical investigation High 37581939
2021 A subpopulation of lateral hypothalamic GABAergic LEPR-expressing neurons (LHLEPR) specifically drives appetitive but not consummatory behaviors. Ablation of LHLEPR neurons prevented appetitive learning in Pavlovian conditioning but did not affect feeding. LHLEPR→VTA projections bidirectionally modulate reward-related behaviors, and chemogenetic inhibition of LHLEPR neurons attenuates cocaine sensitization but not cocaine conditioned place preference. Neuron-specific ablation; Pavlovian conditioning paradigm; optogenetic activation/inhibition; chemogenetic (DREADD) manipulation; food intake and weight measurements Cell reports High 34433027
2016 Leptin binding to OB-R inhibits leptin transport across a human in vitro BBB model (hCMEC/D3 cells) — specifically, an OB-R-neutralizing antibody that blocks leptin-OB-R binding and STAT3 phosphorylation does NOT inhibit leptin transcytosis, establishing that OB-R signaling is not required for leptin transport across human endothelial cells. LRP-2 (megalin) is expressed in these cells and may serve as the primary leptin transporter. In vitro human BBB model (hCMEC/D3); OB-R neutralizing antibody (9F8) treatment; STAT3 phosphorylation assay; transcytosis/transport measurement; endocytosis inhibitor assays; LRP-2 expression analysis Journal of neuroendocrinology Medium 27037668
2018 LepR mutation replacing the three intracellular tyrosine residues (Tyr985, Tyr1077, Tyr1138) with phenylalanine (Y123F mice) causes follicle loss and infertility in female mice, associated with elevated phosphorylation of Akt, mTOR, S6K1, and eIF4B (PTEN/PI3K/mTOR pathway activation) in ovaries, establishing that LepR tyrosine signaling normally suppresses the PTEN/PI3K/mTOR pathway in ovarian follicles. Homologous gene targeting to generate Y123F mice; reproductive phenotyping; AMH measurement; follicle counting; western blotting for pathway components Gynecological endocrinology Medium 30145913
2021 LEPR interacts with ANXA7 (Annexin A7) in hepatocellular carcinoma cells (co-immunoprecipitation), and mechanistically LEPR regulates ERK1/2 and JAK2/STAT3 signaling via ANXA7. Co-immunoprecipitation; western blotting; immunofluorescence; functional assays (proliferation, migration, invasion, apoptosis); siRNA knockdown Cancer cell international Low 33397392
2023 Leptin/obR signaling promotes M1 macrophage polarization via phosphorylation of the long isoform of obR and activation of JNK/STAT3/AKT signaling pathways; leptin-mediated M1 macrophage activity increases CXCL2 production and neutrophil recruitment in obesity-related airway inflammation. db/db obR-deficient mice; obR blockade (Allo-Aca); bone marrow-derived macrophage (BMDM) in vitro experiments; flow cytometry; western blotting; ELISA; BALF cytokine analysis Molecular medicine Medium 37488474
2024 GABAergic LepRGlp1r neurons in the dorsomedial hypothalamus (DMH) mediate suppression of food intake and body weight by a GLP-1R/LepR dual agonist. Ablating Lepr in Glp1r-expressing neurons abrogated the dual agonist's food intake suppression. Reactivation of Glp1r in Lepr neurons on an otherwise Glp1r-null background was sufficient to restore dual agonist efficacy. LepRGlp1r neurons exist in non-human primate DMH. Conditional Lepr ablation in Glp1r neurons; Glp1r reactivation in Lepr neurons; pharmacological dual agonist treatment; food intake and body weight measurement; immunohistochemistry in NHP Science translational medicine High 39630884
2024 GIPR and Lepr strongly co-localize in pancreatic β-cells but not in hypothalamus or hindbrain. Loss of GIPR in Lepr-expressing cells abolishes the superior glycemic effects of GIPR:GLP-1R co-agonism over single GLP-1R agonism, but does not affect body weight or food intake, establishing that LepR+ pancreatic cells (not brain neurons) mediate the glycemic but not anorectic actions of GIP. Single-cell RNA-seq co-expression analysis; Lepr-specific Gipr conditional knockout; metabolic phenotyping; GIP and dual agonist pharmacology in DIO mice Molecular metabolism High 38492844

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Identification and expression cloning of a leptin receptor, OB-R. Cell 2928 8548812
2004 Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 360 15240518
2020 Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. The lancet. Diabetes & endocrinology 351 33137293
1996 Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 252 8690163
1997 Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. The Journal of biological chemistry 251 9020115
1998 Localization of leptin receptor (Ob-R) messenger ribonucleic acid in the rodent hindbrain. Endocrinology 139 9421394
2021 Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function. Nature metabolism 122 34341568
2004 Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Experimental biology and medicine (Maywood, N.J.) 117 14734797
2008 Astrocyte leptin receptor (ObR) and leptin transport in adult-onset obese mice. Endocrinology 109 18292187
2007 CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. The Journal of biological chemistry 106 17387171
2002 A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 89 12032747
2015 Genetic variants in LEP, LEPR, and MC4R explain 30% of severe obesity in children from a consanguineous population. Obesity (Silver Spring, Md.) 80 26179253
2021 Single-cell transcriptomics of LepR-positive skeletal cells reveals heterogeneous stress-dependent stem and progenitor pools. The EMBO journal 78 34957577
1997 Leptin receptor (OB-R) oligomerizes with itself but not with its closely related cytokine signal transducer gp130. FEBS letters 77 9038364
2017 The LepR-mediated leptin transport across brain barriers controls food reward. Molecular metabolism 75 29254602
2011 Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. Proceedings of the National Academy of Sciences of the United States of America 71 22207628
1996 Leptin and OB-R: body weight regulation by a cytokine receptor. Cytokine & growth factor reviews 69 9023054
2009 Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication. Journal of clinical psychopharmacology 60 19142102
2001 LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. European journal of clinical investigation 60 11380591
2002 Leptin receptor (Ob-R) expression is induced in peripheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients. Clinical and experimental immunology 59 12100031
2020 LEPR hypomethylation is significantly associated with gastric cancer in males. Experimental and molecular pathology 58 32659237
2000 Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: potential role in intimal neovascularization. Yonsei medical journal 58 10731922
2001 Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis. Biology of reproduction 57 11159367
2023 Leptin/obR signaling exacerbates obesity-related neutrophilic airway inflammation through inflammatory M1 macrophages. Molecular medicine (Cambridge, Mass.) 56 37488474
2001 Expression of leptin (Ob) and leptin receptor (Ob-R) in human fibroblasts: regulation of leptin secretion by insulin. The Journal of clinical endocrinology and metabolism 56 11549696
2020 LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration. Journal of dental research 54 32585118
2005 Polymorphisms in the leptin receptor (LEPR)--putative association with obesity and T2DM. Journal of human genetics 54 16333525
2011 Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study. PloS one 52 22028824
2023 Lepr-Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 50 37553778
2023 Suppression of food intake by Glp1r/Lepr-coexpressing neurons prevents obesity in mouse models. The Journal of clinical investigation 50 37581939
2022 Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide. Journal of the Endocrine Society 48 35528826
2017 HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway. Stem cell reports 46 29249663
1997 Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130. FEBS letters 46 9003804
2018 Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children. Endocrine 45 29679223
2010 Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype. Mammalian genome : official journal of the International Mammalian Genome Society 45 21128076
2006 LEPR, ADBR3, IRS-1 and 5-HTT genes polymorphisms do not associate with obesity. Endocrine journal 45 17124363
2010 Investigation of porcine FABP3 and LEPR gene polymorphisms and mRNA expression for variation in intramuscular fat content. Molecular biology reports 44 20300864
2021 Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors. Cell reports 43 34433027
2014 Hypoxia inducible factor (HIF)-1α directly activates leptin receptor (Ob-R) in pancreatic cancer cells. Cancer letters 42 25130171
2006 Expression pattern of leptin and leptin receptor (OB-R) in human gastric cancer. World journal of gastroenterology 39 17006991
2016 Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis. Journal of diabetes research 38 27195302
2011 Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36 21887553
2014 The expression of LEP, LEPR, IGF1 and IL10 in obesity and the relationship with microRNAs. PloS one 35 24690978
2014 Correlation analysis between the expressions of leptin and its receptor (ObR) and clinicopathology in endometrial cancer. Cancer biomarkers : section A of Disease markers 34 25171477
2022 Lepr+ mesenchymal cells sense diet to modulate intestinal stem/progenitor cells via Leptin-Igf1 axis. Cell research 32 35296796
2017 LepR+ cells dispute hegemony with Gli1+ cells in bone marrow fibrosis. Cell cycle (Georgetown, Tex.) 31 28976809
2017 LEP rs7799039, LEPR rs1137101, and ADIPOQ rs2241766 and 1501299 Polymorphisms Are Associated With Obesity and Chemotherapy Response in Mexican Women With Breast Cancer. Clinical breast cancer 29 28416193
1999 Combination of polymorphisms in OB-R and the OB gene associated with insulin resistance in Nauruan males. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 29 10490782
2019 The LepRdb/db mice model for studying glycation in the context of diabetes. Diabetes/metabolism research and reviews 27 30467969
2009 Effects of leptin on in vitro maturation, fertilization and embryonic cleavage after ICSI and early developmental expression of leptin (Ob) and leptin receptor (ObR) proteins in the horse. Reproductive biology and endocrinology : RB&E 27 19835605
2015 Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid. The international journal of neuropsychopharmacology 26 25740917
2022 Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency. Orphanet journal of rare diseases 25 35123544
2021 Associations of MC4R, LEP, and LEPR Polymorphisms with Obesity-Related Parameters in Childhood and Adulthood. Genes 25 34205732
2008 Leptin receptor/CD295 is upregulated on primary human mesenchymal stem cells of advancing biological age and distinctly marks the subpopulation of dying cells. Experimental gerontology 25 18573328
2001 Mechanisms for LEPR-mediated regulation of leptin expression in brown and white adipocytes in rat pups. Physiological genomics 25 11160998
2013 Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis. PloS one 24 24146750
2019 Cryo-EM structure of pleconaril-resistant rhinovirus-B5 complexed to the antiviral OBR-5-340 reveals unexpected binding site. Proceedings of the National Academy of Sciences of the United States of America 22 31462495
2016 Prevalence of mutations in LEP, LEPR, and MC4R genes in individuals with severe obesity. Genetics and molecular research : GMR 22 27706562
2013 Adenovirus-mediated interference of FABP4 regulates mRNA expression of ADIPOQ, LEP and LEPR in bovine adipocytes. Genetics and molecular research : GMR 22 23315880
2008 Novel SNPs of the bovine LEPR gene and their association with growth traits. Biochemical genetics 22 18807168
2024 Glp1r-Lepr coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist. Science translational medicine 21 39630884
2022 Understanding the Patient Experience of Hunger and Improved Quality of Life with Setmelanotide Treatment in POMC and LEPR Deficiencies. Advances in therapy 21 35192151
2011 Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis. Molecular biology reports 21 21698367
2008 Comparison of STAT3 with HIF-1alpha, Ob and ObR expressions in human endometrioid adenocarcinomas. Tissue & cell 21 18579174
2016 Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across a Human Blood-Brain Barrier Model. Journal of neuroendocrinology 20 27037668
2008 Leptin and the obesity receptor (OB-R) in the small intestine and colon: a colocalization study. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 18413648
2020 Irisin Improves Myocardial Performance and Attenuates Insulin Resistance in Spontaneous Mutation (Lepr ) Mice. Frontiers in pharmacology 19 32581784
2019 Fat mass and obesity-associated (FTO) and leptin receptor (LEPR) gene polymorphisms in Egyptian obese subjects. Archives of physiology and biochemistry 19 30767572
2017 Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas. Oncotarget 19 29312594
2014 The association of 5-HT2A, 5-HTT, and LEPR polymorphisms with obstructive sleep apnea syndrome: a systematic review and meta-analysis. PloS one 19 24755731
2023 LepR+ niche cell-derived AREG compromises hematopoietic stem cell maintenance under conditions of DNA repair deficiency and aging. Blood 18 37584437
2021 Leptin Receptor (LEPR) promotes proliferation, migration, and invasion and inhibits apoptosis in hepatocellular carcinoma by regulating ANXA7. Cancer cell international 18 33397392
2012 Role of leptin receptor (LEPR) gene polymorphisms and haplotypes in susceptibility to hepatocellular carcinoma in subjects with chronic hepatitis B virus infection. Molecular diagnosis & therapy 17 23090836
2010 Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication. Psychiatric genetics 17 20562674
2021 PP2A in LepR+ mesenchymal stem cells contributes to embryonic and postnatal endochondral ossification through Runx2 dephosphorylation. Communications biology 16 34079065
2018 A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk. PloS one 16 29293570
2017 LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: a meta-analysis of 3,367 subjects. Oncotarget 16 28977915
2011 ADRB2 and LEPR gene polymorphisms: synergistic effects on the risk of obesity in Japanese. Obesity (Silver Spring, Md.) 16 21233812
2024 Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics. Journal of dental research 15 39104161
2018 Genetic polymorphisms of HTR2C, LEP and LEPR on metabolic syndromes in patients treated with atypical antipsychotic drugs. The Journal of pharmacy and pharmacology 14 29441581
2022 Association analysis between novel variants in LEPR gene and litter size in Mongolia and ujimqin sheep breeds. Theriogenology 13 35228133
2022 Quercetin ameliorates salivary gland apoptosis and inflammation in primary Sjögren's syndrome through regulation of the leptin/OB-R signaling. Drug development research 13 35749642
2021 Promoter Methylation of and before and after Bariatric Surgery: A Cross-Sectional Study. Obesity facts 13 33530087
2019 Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI-SDS-A case series. Pediatric obesity 13 31670905
2024 Single-cell sequencing reveals that specnuezhenide protects against osteoporosis via activation of METTL3 in LEPR+ BMSCs. European journal of pharmacology 12 39154827
2023 Xiaoyaosan ameliorates depressive-like behavior and susceptibility to glucose intolerance in rat: involvement of LepR-STAT3/PI3K pathway in hypothalamic arcuate nucleus. BMC complementary medicine and therapies 12 37046230
2023 Galantamine improves glycemic control and diabetic nephropathy in Leprdb/db mice. Scientific reports 12 37731032
2020 Investigation of Leptin and its receptor (LEPR) for single nucleotide polymorphisms in colorectal cancer: a case-control study involving 2,306 subjects. American journal of translational research 12 32774722
2018 Identification of novel LEPR mutations in Pakistani families with morbid childhood obesity. BMC medical genetics 12 30442103
2017 LEPR gene polymorphism and plasma soluble leptin receptor levels are associated with polycystic ovary syndrome in Han Chinese women. Personalized medicine 12 29749830
2022 Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing. Journal of pediatric endocrinology & metabolism : JPEM 11 35801948
2021 A novel compound heterozygous leptin receptor mutation causes more severe obesity than in Leprdb/db mice. Journal of lipid research 11 34390703
2019 Clinical significance of Leptin receptor (LEPR) and Endoglin (CD105) expressions in colorectal adenocarcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 11 31983119
2017 Leptin/OB-R pathway promotes IL-4 secretion from B lymphocytes and induces salivary gland epithelial cell apoptosis in Sjögren's syndrome. Oncotarget 11 28969001
2009 Inflammatory state and stress condition in weight-lowering Lys109Arg LEPR gene polymorphism carriers. Archives of medical research 11 19608021
2004 Association of Ob-R gene polymorphism and insulin resistance in Japanese men. Metabolism: clinical and experimental 11 15131772
2024 Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice. Molecular metabolism 10 38492844
2024 The Long Non-Coding RNA Obesity-Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 38704700
2021 Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis. Asian Pacific journal of cancer prevention : APJCP 10 34452542
2018 Follicle loss and PTEN/PI3K/mTOR signaling pathway activated in LepR-mutated mice. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 10 30145913

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