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Gene Review

LEPR  -  leptin receptor

Homo sapiens

Synonyms: CD295, DB, HuB219, LEP-R, LEPRD, ...
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Disease relevance of LEPR


Psychiatry related information on LEPR

  • 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) [5].
  • The aim of our study was to measure S-LEPR levels in patients with anorexia nervosa (AN) before and 6 weeks after partial refeeding [6].
  • Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum [7].
  • These data support a critical role for VTA Lepr in regulating feeding behavior and provide functional evidence for direct action of a peripheral metabolic signal on VTA dopamine neurons [8].
  • Fluorescent analogues (DB1 and TA1) of the secondary metabolites didemnin B (DB) and tamandarin A (TA) were synthesized to investigate the potential chemical defense mechanisms of tunicates in the family Didemnidae [9].

High impact information on LEPR

  • OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus [10].
  • These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling [11].
  • Obesity: leptin receptor weighs in [12].
  • Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R [13].
  • Here, an OB-R variant was found in human hepatic cells [13].

Chemical compound and disease context of LEPR


Biological context of LEPR


Anatomical context of LEPR

  • 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 [22].
  • 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-T15 insulinoma cells [23].
  • Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice [24].
  • Using PC12 cells as an in vitro model system, we have identified a series of transcripts induced through activation of the leptin receptor [25].
  • 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 [26].

Associations of LEPR with chemical compounds

  • Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals [5].
  • Serum bone-specific alkaline phosphatase (S-BAP) was associated with LEPR genotypes (P = 0.05) and urinary C-terminal telopeptides of type I collagen (U-CTX) were associated with leptin levels (P = 0.03), independently from age, fat mass and free estradiol [27].
  • Other significant linkages observed were between LEP and waist/hip ratio (P = 0.010), total cholesterol (P = 0.030), and HDL cholesterol (P = 0.026) and between LEPR and fasting blood glucose (P = 0.018) and diastolic blood pressure (P = 0.003) [28].
  • Furthermore, the sequence motifs surrounding the three tyrosine residues are conserved in LEPR from mammals, birds and in a LEPR-like cytokine receptor from pufferfish [23].
  • METHODS: Anthropometric variables, serum leptin, S-LEPR, insulin, cortisol and TNF-alpha were measured in 15 AN patients before and after partial refeeding and 15 healthy control women [6].

Physical interactions of LEPR


Enzymatic interactions of LEPR


Co-localisations of LEPR


Regulatory relationships of LEPR


Other interactions of LEPR

  • While multiple alternatively spliced LR isoforms exist, only the long (LRb) form associates with the Janus kinase 2 (Jak2) tyrosine kinase to mediate intracellular signaling [40].
  • It has been demonstrated that the SH2 domain-containing tyrosine phosphatase 2 (SHP-2) negatively regulates STAT3-mediated transcriptional activation through long form leptin receptor (OBRb) [41].
  • CONCLUSION: Only variations in the ADRB2 gene and LEPR gene, may contribute to susceptibility to weight gain [42].
  • Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival [43].
  • The structure of leptin receptor (OB-R) is highly homologous to that of gp130, the common signal transducing receptor component for the interleukin-6 family of cytokines [44].

Analytical, diagnostic and therapeutic context of LEPR

  • There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups [45].
  • 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 [46].
  • DESIGN: This was a cross-sectional study to investigate the impact of the Q223R polymorphism of the LEPR gene on insulin sensitivity [47].
  • CONCLUSIONS: In women, genetic variations at the LEPR gene level are associated with overweight and fat mass in a cross sectional study and with response to low calorie diet in an intervention study [4].
  • We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies [48].


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  2. Hypertension in obesity and the leptin receptor gene locus. Rosmond, R., Chagnon, Y.C., Holm, G., Chagnon, M., Pérusse, L., Lindell, K., Carlsson, B., Bouchard, C., Björntorp, P. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  3. Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults. van Rossum, C.T., Hoebee, B., van Baak, M.A., Mars, M., Saris, W.H., Seidell, J.C. Obes. Res. (2003) [Pubmed]
  4. LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Mammès, O., Aubert, R., Betoulle, D., Péan, F., Herbeth, B., Visvikis, S., Siest, G., Fumeron, F. Eur. J. Clin. Invest. (2001) [Pubmed]
  5. Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study. Lakka, T.A., Rankinen, T., Weisnagel, S.J., Chagnon, Y.C., Lakka, H.M., Ukkola, O., Boulé, N., Rice, T., Leon, A.S., Skinner, J.S., Wilmore, J.H., Rao, D.C., Bergman, R., Bouchard, C. Diabetes (2004) [Pubmed]
  6. Soluble leptin receptor levels in patients with anorexia nervosa. Krizova, J., Papezova, H., Haluzikova, D., Parizkova, J., Jiskra, J., Kotrlikova, E., Haas, T., Haluzik, M. Endocr. Res. (2002) [Pubmed]
  7. Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum. Monteleone, P., Fabrazzo, M., Tortorella, A., Fuschino, A., Maj, M. Mol. Psychiatry (2002) [Pubmed]
  8. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Hommel, J.D., Trinko, R., Sears, R.M., Georgescu, D., Liu, Z.W., Gao, X.B., Thurmon, J.J., Marinelli, M., Dileone, R.J. Neuron (2006) [Pubmed]
  9. Chemical defense in ascidians of the didemnidae family. Joullié, M.M., Leonard, M.S., Portonovo, P., Liang, B., Ding, X., La Clair, J.J. Bioconjug. Chem. (2003) [Pubmed]
  10. Identification and expression cloning of a leptin receptor, OB-R. Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., Smutko, J.S., Mays, G.G., Wool, E.A., Monroe, C.A., Tepper, R.I. Cell (1995) [Pubmed]
  11. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C.S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C.A., Roberts, J.L., Gao, X.B., Mobbs, C., Shulman, G.I., Diano, S., Horvath, T.L. Nat. Med. (2007) [Pubmed]
  12. Obesity: leptin receptor weighs in. Barinaga, M. Science (1996) [Pubmed]
  13. Modulation of insulin activities by leptin. Cohen, B., Novick, D., Rubinstein, M. Science (1996) [Pubmed]
  14. Diencephalic syndrome due to hypothalamic tumor: a model of the relationship between weight and puberty onset. Brauner, R., Trivin, C., Zerah, M., Souberbielle, J.C., Doz, F., Kalifa, C., Sainte-Rose, C. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  15. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism. Stefan, N., Vozarova, B., Del Parigi, A., Ossowski, V., Thompson, D.B., Hanson, R.L., Ravussin, E., Tataranni, P.A. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  16. Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery. Haas, V., Onur, S., Paul, T., Nutzinger, D.O., Bosy-Westphal, A., Hauer, M., Brabant, G., Klein, H., Müller, M.J. Am. J. Clin. Nutr. (2005) [Pubmed]
  17. Seasonally inappropriate body weight induced by food restriction: effect on hypothalamic gene expression in male Siberian hamsters. Mercer, J.G., Moar, K.M., Logie, T.J., Findlay, P.A., Adam, C.L., Morgan, P.J. Endocrinology (2001) [Pubmed]
  18. The metabolic syndrome--a neuroendocrine disorder? Björntorp, P., Rosmond, R. Br. J. Nutr. (2000) [Pubmed]
  19. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Thompson, D.B., Ravussin, E., Bennett, P.H., Bogardus, C. Hum. Mol. Genet. (1997) [Pubmed]
  20. Xenoduplex analysis--a method for comparative gene mapping using hybrid panels. Marklund, L., Jeon, J.T., Andersson, L. Genome Res. (1998) [Pubmed]
  21. Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women. Wauters, M., Considine, R.V., Chagnon, M., Mertens, I., Rankinen, T., Bouchard, C., Van Gaal, L.F. Obes. Res. (2002) [Pubmed]
  22. Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Woo, H.Y., Park, H., Ki, C.S., Park, Y.L., Bae, W.G. Cancer Lett. (2006) [Pubmed]
  23. Pleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines. Hekerman, P., Zeidler, J., Bamberg-Lemper, S., Knobelspies, H., Lavens, D., Tavernier, J., Joost, H.G., Becker, W. FEBS J. (2005) [Pubmed]
  24. Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Lam, Q.L., Liu, S., Cao, X., Lu, L. Eur. J. Immunol. (2006) [Pubmed]
  25. Identification and expression analysis of leptin-regulated immediate early response and late target genes. Waelput, W., Verhee, A., Broekaert, D., Eyckerman, S., Vandekerckhove, J., Beattie, J.H., Tavernier, J. Biochem. J. (2000) [Pubmed]
  26. 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. Keen-Rhinehart, E., Kalra, S.P., Kalra, P.S. Biol. Reprod. (2004) [Pubmed]
  27. Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Crabbe, P., Goemaere, S., Zmierczak, H., Van Pottelbergh, I., De Bacquer, D., Kaufman, J.M. Eur. J. Endocrinol. (2006) [Pubmed]
  28. Linkage analysis of candidate obesity genes among the Mexican-American population of Starr County, Texas. Bray, M.S., Boerwinkle, E., Hanis, C.L. Genet. Epidemiol. (1999) [Pubmed]
  29. Transduction of leptin growth signals in placental cells is independent of JAK-STAT activation. Caüzac, M., Czuba, D., Girard, J., Hauguel-de Mouzon, S. Placenta (2003) [Pubmed]
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  32. A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells. Gonzalez, R.R., Leavis, P.C. Endocrine (2003) [Pubmed]
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  39. Estrogen receptor alpha gene polymorphisms Pvu II and Xba I influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men. Koh, J.M., Kim, D.J., Hong, J.S., Park, J.Y., Lee, K.U., Kim, S.Y., Kim, G.S. Eur. J. Endocrinol. (2002) [Pubmed]
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  41. Vanadate enhances leptin-induced activation of JAK/STAT pathway in CHO cells. Kita, A., Uotani, S., Kuwahara, H., Takahashi, R., Oshima, K., Yamasaki, H., Mizuguchi, H., Hayakawa, T., Nagayama, Y., Yamaguchi, Y., Eguchi, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  42. Genetic factors as predictors of weight gain in young adult Dutch men and women. van Rossum, C.T., Hoebee, B., Seidell, J.C., Bouchard, C., van Baak, M.A., de Groot, C.P., Chagnon, M., de Graaf, C., Saris, W.H. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  43. Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma. Snoussi, K., Strosberg, A.D., Bouaouina, N., Ben Ahmed, S., Helal, A.N., Chouchane, L. BMC Cancer (2006) [Pubmed]
  44. Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130. Nakashima, K., Narazaki, M., Taga, T. FEBS Lett. (1997) [Pubmed]
  45. G-2548A Polymorphism of the Leptin Gene Is Correlated with Extreme Obesity in Taiwanese Aborigines. Wang, T.N., Huang, M.C., Chang, W.T., Ko, A.M., Tsai, E.M., Liu, C.S., Lee, C.H., Ko, Y.C. Obes. Res. (2006) [Pubmed]
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  47. Association of leptin receptor polymorphism with insulin resistance. Chiu, K.C., Chu, A., Chuang, L.M., Saad, M.F. Eur. J. Endocrinol. (2004) [Pubmed]
  48. Changes in Placental Adipocytokine Gene Expression Associated with Gestational Diabetes MellitusA. Meller, M., Qiu, C., Vadachkoria, S., Abetew, D.F., Luthy, D.A., Williams, M.A. Physiological research / Academia Scientiarum Bohemoslovaca. (2006) [Pubmed]
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