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Gene Review

LEP  -  leptin

Homo sapiens

Synonyms: LEPD, Leptin, OB, OBS, Obese protein, ...
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Disease relevance of LEP

  • Among those with the LEP 19G allele, an increased risk estimate was found for all NHL [OR = 1.6, confidence interval (CI) 1.1-2.3], DLCL (OR = 1.6, CI 0.86-3.0), and FL lymphoma (OR = 1.9, CI 0.98-3.6) [1].
  • Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR = 0.7, 95% CI 0.5-1.0) and increased with LEP -2548GA (OR = 1.3, 95% CI 1.0-1.7) and -2548AA (OR = 1.4, 95% CI 1.0-1.9), particularly for follicular lymphoma [2].
  • The present study is to investigate whether chromosomal regions 7q and 11q, which contain LEP and UCP2/UCP3, respectively, can be excluded for linkage with obesity phenotypes [3].
  • A modest elevated spina bifida risk, irrespective of maternal BMI, was observed for two LEP microsatellite alleles (257 and 271) [4].
  • 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 [5].
  • Hyperleptinemia and high FF leptin are important pathologies of PCOS with infertility [6].
  • Following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus [7].

Psychiatry related information on LEP

  • The inverse association between the Q223R polymorphism and obesity (OR = 0.62; 95% CI: 0.39-0.99) remained significant even after additional adjustment for education, tobacco smoking, alcohol, physical activity, origin of the obese patient, and the -2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32-0.89) [8].
  • The circadian rhythm of several plasma hormones (prolactin, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and melatonin) was simultaneously evaluated in 23 women with anorexia nervosa (AN), in 27 obese (OB) women, and in gender and age-matched healthy controls [9].
  • Finally, we discuss the possibility that leptin, the OB gene product, may be the link of some of these endocrine abnormalities, and that its abnormal secretion during stroke may contribute to the eating disorders and poor nutritional status often seen in these patients [10].
  • Reaction time, subjective pain intensities and evoked vertex potentials to laser (LEP) and electrical (SEP) stimuli were recorded and compared with auditory evoked potentials (AEP) [11].
  • The MMPI profiles of the obese subjects were compared to those of a general medical population of 50,000 patients seen in the Department of Internal Medicine at the Mayo Clinic. Obese male subjects had significantly higher scores on the F and MA scales [12].

High impact information on LEP


Chemical compound and disease context of LEP


Biological context of LEP


Anatomical context of LEP

  • Northern blot analysis revealed that OB RNA is present at a high level in adipose tissue but at much lower levels in placenta and heart [26].
  • No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects [27].
  • Attention has focused on the hypothalamus as its potential site of action, but OB could also act on other brain regions [28].
  • OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF-I axis, adrenal and thyroid activity [29].
  • 3H-ouabain concentration on erythrocytes (OBS) was also determined [30].

Associations of LEP with chemical compounds

  • Therefore, the objective of the current study was to determine the mechanism of estrogen action on LEP promoter activation in divergent cell types [31].
  • In OB women, IGF-I concentrations positively correlated with PRL (r = 0.31), testosterone (r = 0.30), androstenedione (r = 0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r = 0.41) [32].
  • Simultaneous evaluation of different neuroendocrine rhythms in these three groups revealed similar circadian abnormalities, (namely daytime persistence of melatonin secretion in AN and OB, and similar cortisol profile changes in AN and BN), together with evidence of internal desynchronization among the different bioperiodic functions [33].
  • The arginine-induced insulin release in HP and OB was similar (4219.4 +/- 631.7 and 4107.3 +/- 643.2 mU x min x l(-1), respectively), both being higher (p < 0.02) than in NS (2178.1 +/- 290.9 mU x min x l(-1) [34].
  • RESULTS: Obese rats had significantly higher (P < 0.05) body and liver weight, as well as plasma insulin, lactate, cholesterol, triglyceride and tumor necrosis factor (TNF)-alpha compared to their Ln counterparts [35].
  • Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression [36].

Regulatory relationships of LEP


Other interactions of LEP

  • Basal ghrelin levels in NW were higher than in OB (P < 0.05) [43].
  • METHOD: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps [44].
  • These results demonstrate that OB protein can functionally antagonize and dominate the actions of exogenous NPY on feeding [45].
  • Our results suggest that the LEP and UCP2/UCP3 genes are unlikely to have a substantial effect on variation in obesity phenotypes in this particular US Caucasian population [3].
  • Circulating Serum Adiponectin Concentrations do not Differ between Obese and Non-obese Caucasians and are Unrelated to Insulin Sensitivity [46].

Analytical, diagnostic and therapeutic context of LEP

  • 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 [5].
  • OBJECTIVES: Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3' UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans [47].
  • RESEARCH METHODS AND PROCEDURES: Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients [27].
  • Our objective has been to conduct a population-based case-control study to estimate the risk of obesity arising from the -2548G > A and Q223R polymorphisms in the LEP and LEPR genes, respectively [8].
  • To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families [48].


  1. Body mass index, leptin and leptin receptor polymorphisms, and non-hodgkin lymphoma. Skibola, C.F., Holly, E.A., Forrest, M.S., Hubbard, A., Bracci, P.M., Skibola, D.R., Hegedus, C., Smith, M.T. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  2. Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms. Willett, E.V., Skibola, C.F., Adamson, P., Skibola, D.R., Morgan, G.J., Smith, M.T., Roman, E. Br. J. Cancer (2005) [Pubmed]
  3. Linkage exclusion analysis of two candidate regions on chromosomes 7 and 11: leptin and UCP2/UCP3 are not QTLs for obesity in US Caucasians. Guo, J.J., Liu, Y.J., Li, M.X., Yang, Y.J., Recker, R.R., Deng, H.W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  4. Microsatellites proximal to leptin and leptin receptor as risk factors for spina bifida. Shaw, G.M., Barber, R., Todoroff, K., Lammer, E.J., Finnell, R.H. Teratology (2000) [Pubmed]
  5. 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]
  6. Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome. Li, M.G., Ding, G.L., Chen, X.J., Lu, X.P., Dong, L.J., Dong, M.Y., Yang, X.F., Lu, X.E., Huang, H.F. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  7. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. Rosenbaum, M., Sy, M., Pavlovich, K., Leibel, R.L., Hirsch, J. J. Clin. Invest. (2008) [Pubmed]
  8. Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain. Portol??s, O., Sorl??, J.V., Franc??s, F., Coltell, O., Gonz??lez, J.I., S??iz, C., Corella, D. Eur. J. Epidemiol. (2006) [Pubmed]
  9. Hormonal circadian rhythms in eating disorders. Ferrari, E., Fraschini, F., Brambilla, F. Biol. Psychiatry (1990) [Pubmed]
  10. Endocrine abnormalities and outcome of ischaemic stroke. Franceschini, R., Tenconi, G.L., Zoppoli, F., Barreca, T. Biomed. Pharmacother. (2001) [Pubmed]
  11. Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by evoked potentials. Roth, D., Petersen-Felix, S., Bak, P., Arendt-Nielsen, L., Fischer, M., Bjerring, P., Zbinden, A.M. British journal of anaesthesia. (1996) [Pubmed]
  12. Personality characteristics in obesity: relation of MMPI profile and age of onset of obesity to success in weight reduction. Johnson, S.F., Swenson, W.M., Gastineau, C.F. Am. J. Clin. Nutr. (1976) [Pubmed]
  13. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. Nestler, J.E., Jakubowicz, D.J., Evans, W.S., Pasquali, R. N. Engl. J. Med. (1998) [Pubmed]
  14. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. Khan, M.A., Herzog, C.A., St Peter, J.V., Hartley, G.G., Madlon-Kay, R., Dick, C.D., Asinger, R.W., Vessey, J.T. N. Engl. J. Med. (1998) [Pubmed]
  15. Predicting obesity in young adulthood from childhood and parental obesity. Whitaker, R.C., Wright, J.A., Pepe, M.S., Seidel, K.D., Dietz, W.H. N. Engl. J. Med. (1997) [Pubmed]
  16. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Schwartz, M.W., Peskind, E., Raskind, M., Boyko, E.J., Porte, D. Nat. Med. (1996) [Pubmed]
  17. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., Burn, P. Science (1995) [Pubmed]
  18. ENPP1 Variants and Haplotypes Predispose to Early Onset Obesity and Impaired Glucose and Insulin Metabolism in German Obese Children. B??ttcher, Y., K??rner, A., Reinehr, T., Enigk, B., Kiess, W., Stumvoll, M., Kovacs, P. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  19. Chronic Treatment with Pioglitazone Does Not Protect Obese Patients with Diabetes Mellitus Type II from Free Fatty Acid-Induced Insulin Resistance. Serlie, M.J., Allick, G., Groener, J.E., Ackermans, M.T., Heijligenberg, R., Voermans, B.C., Aerts, J.M., Meijer, A.J., Sauerwein, H.P. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  20. Relationship of Serum Interleukin-6 and Tumor Necrosis Factor alpha Levels with Abdominal Fat Distribution Evaluated by Ultrasonography in Overweight or Obese Postmenopausal Women. Fenkci, S., Rota, S., Sabir, N., Sermez, Y., Guclu, A., Akdag, B. J. Investig. Med. (2006) [Pubmed]
  21. Low bone mass in premenopausal chronic dieting obese women. Bacon, L., Stern, J.S., Keim, N.L., Van Loan, M.D. European journal of clinical nutrition. (2004) [Pubmed]
  22. Hormonal abnormalities in obesity. Zumoff, B. Acta Med. Scand. Suppl. (1988) [Pubmed]
  23. 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]
  24. Fluorescence resonance energy transfer (FRET) microscopy in living cells as a novel tool for the study of cytokine action. Gertler, A., Biener, E., Ramanujan, K.V., Djiane, J., Herman, B. J. Dairy Res. (2005) [Pubmed]
  25. Localization of leptin receptor in the human brain. Couce, M.E., Burguera, B., Parisi, J.E., Jensen, M.D., Lloyd, R.V. Neuroendocrinology (1997) [Pubmed]
  26. The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7. Green, E.D., Maffei, M., Braden, V.V., Proenca, R., DeSilva, U., Zhang, Y., Chua, S.C., Leibel, R.L., Weissenbach, J., Friedman, J.M. Genome Res. (1995) [Pubmed]
  27. Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals. McAinch, A.J., Steinberg, G.R., Mollica, J., O'brien, P.E., Dixon, J.B., Macaulay, S.L., Kemp, B.E., Cameron-Smith, D. Obesity (Silver Spring, Md.) (2006) [Pubmed]
  28. Corticotropin-releasing factor and adrenocorticotrophic hormone as potential central mediators of OB effects. Raber, J., Chen, S., Mucke, L., Feng, L. J. Biol. Chem. (1997) [Pubmed]
  29. Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function. Lanfranco, F., Gianotti, L., Pivetti, S., Navone, F., Rossetto, R., Tassone, F., Gai, V., Ghigo, E., Maccario, M. Clin. Endocrinol. (Oxf) (2004) [Pubmed]
  30. Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent. Sophocleous, A., Elmatzoglou, I., Souvatzoglou, A. J. Endocrinol. Invest. (2003) [Pubmed]
  31. Effects of estrogen on leptin gene promoter activation in MCF-7 breast cancer and JEG-3 choriocarcinoma cells: selective regulation via estrogen receptors alpha and beta. O'Neil, J.S., Burow, M.E., Green, A.E., McLachlan, J.A., Henson, M.C. Mol. Cell. Endocrinol. (2001) [Pubmed]
  32. Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients. Maccario, M., Ramunni, J., Oleandri, S.E., Procopio, M., Grottoli, S., Rossetto, R., Savio, P., Aimaretti, G., Camanni, F., Ghigo, E. Int. J. Obes. Relat. Metab. Disord. (1999) [Pubmed]
  33. Circadian neuroendocrine functions in disorders of eating behavior. Ferrari, E., Magri, F., Pontiggia, B., Rondanelli, M., Fioravanti, M., Solerte, S.B., Severgnini, S. Eating and weight disorders : EWD. (1997) [Pubmed]
  34. Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity. Maccario, M., Grottoli, S., Razzore, P., Procopio, M., Oleandri, S.E., Ciccarelli, E., Camanni, F., Ghigo, E. Eur. J. Endocrinol. (1996) [Pubmed]
  35. Alleviation of hepatic steatosis accompanied by modulation of plasma and liver TNF-alpha levels by Trigonella foenum graecum (fenugreek) seeds in Zucker obese (fa/fa) rats. Raju, J., Bird, R.P. International journal of obesity (2005) (2006) [Pubmed]
  36. Up-regulation of placental leptin by human chorionic gonadotropin. Maymó, J.L., Pérez Pérez, A., Sánchez-Margalet, V., Dueñas, J.L., Calvo, J.C., Varone, C.L. Endocrinology (2009) [Pubmed]
  37. Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women. Buijs, M.M., Romijn, J.A., Burggraaf, J., De Kam, M.L., Cohen, A.F., Frölich, M., Stellaard, F., Meinders, A.E., Pijl, H. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  38. Effects of transforming growth factor beta (TGF beta) and 1,25 dihydroxyvitamin D3 on the function, cytochemistry and morphology of normal human osteoblast-like cells. Ingram, R.T., Bonde, S.K., Riggs, B.L., Fitzpatrick, L.A. Differentiation (1994) [Pubmed]
  39. Anterior pituitary corticotropes of adrenalectomized, leptin-administered rats. Malendowicz, L.K., Ziólkowska, A., Trejter, M. Pituitary (2001) [Pubmed]
  40. A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families. Gaukrodger, N., Mayosi, B.M., Imrie, H., Avery, P., Baker, M., Connell, J.M., Watkins, H., Farrall, M., Keavney, B. J. Med. Genet. (2005) [Pubmed]
  41. Serum Amyloid A and Obstructive Sleep Apnea Syndrome before and after Surgically-Induced Weight Loss in Morbidly Obese Subjects. Poitou, C., Coupaye, M., Laaban, J.P., Coussieu, C., Bedel, J.F., Bouillot, J.L., Basdevant, A., Cl??ment, K., Oppert, J.M. Obesity surgery : the official journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand (2006) [Pubmed]
  42. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. Saxena, N.K., Vertino, P.M., Anania, F.A., Sharma, D. J. Biol. Chem. (2007) [Pubmed]
  43. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity. Tassone, F., Broglio, F., Destefanis, S., Rovere, S., Benso, A., Gottero, C., Prodam, F., Rossetto, R., Gauna, C., van der Lely, A.J., Ghigo, E., Maccario, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  44. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan, M.A., Thorburn, A.W., Fam, B., Summers, R., Conway-Campbell, B., Waters, M.J., Ng, F.M. Int. J. Obes. Relat. Metab. Disord. (2001) [Pubmed]
  45. Brain administration of OB protein (leptin) inhibits neuropeptide-Y-induced feeding in ob/ob mice. Smith, F.J., Campfield, L.A., Moschera, J.A., Bailon, P.S., Burn, P. Regul. Pept. (1998) [Pubmed]
  46. Circulating Serum Adiponectin Concentrations do not Differ between Obese and Non-obese Caucasians and are Unrelated to Insulin Sensitivity. Owecki, M., Miczke, A., Pupek-Musialik, D., Bryl, W., Cymerys, M., Nikisch, E., Sowiński, J. Horm. Metab. Res. (2007) [Pubmed]
  47. Human leptin locus (LEP) alleles and BMI in Samoans. McGarvey, S.T., Forrest, W., Weeks, D.E., Sun, G., Smelser, D., Tufa, J., Viali, S., Deka, R. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  48. Indication for linkage of the human OB gene region with extreme obesity. Clement, K., Garner, C., Hager, J., Philippi, A., LeDuc, C., Carey, A., Harris, T.J., Jury, C., Cardon, L.R., Basdevant, A., Demenais, F., Guy-Grand, B., North, M., Froguel, P. Diabetes (1996) [Pubmed]
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