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Gene Review

Lep  -  leptin

Rattus norvegicus

Synonyms: Leptin, OB, Ob, Obesity factor, obese
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Disease relevance of Lep

  • The circulating peptide leptin, which is the product of the ob gene, provides feedback information on the size of fat stores to central Ob receptors that control food intake and body-weight homeostasis [1].
  • To investigate the physiological role of leptin in the control of meal size and the response to satiety signals, and to identify brain areas mediating this effect, we studied Koletsky (fa(k)/fa(k)) rats, which develop severe obesity due to the genetic absence of leptin receptors [2].
  • This process could contribute to the limiting of hyperphagia, primarily when leptin signaling is altered, as in the obese state [3].
  • To determine whether these effects may be altered in hypertension, we assessed the effect of leptin on angiotensin II-induced vascular response in the aorta of 10-week-old spontaneously hypertensive rats (SHR) [4].
  • These data raise the possibility that high leptin levels may contribute to infertility in some women with PCOS by counteracting the sensitizing effects of IGF-I in dominant follicles [5].
  • Our data showed that maternal undernutrition drastically reduces the postnatal surge of plasma leptin, disturbing particularly the hypothalamic wiring as well as the gene expression of the anorexigenic POMC neurons in male rat pups [6].

Psychiatry related information on Lep


High impact information on Lep


Chemical compound and disease context of Lep


Biological context of Lep


Anatomical context of Lep


Associations of Lep with chemical compounds

  • These data indicate that a supply of calories via glucose infusion induces a hypophagic response independent of leptin signaling in the rat, and support the hypothesis that a rise in central malonyl-CoA, triggered by increased glucose and insulin concentrations, participates in this adaptation [3].
  • Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01) [22].
  • Insulin alone (P < 0.01), but not leptin, increased autophosphorylation of nonreceptor tyrosine kinases (pp59(Lyn) + pp125(Fak)) [23].
  • Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells [5].
  • In order to address this question, the present study examined the effects of direct intrahypothalamic perfusions with leptin on the in vivo release of GnRH in ovarian steroid-primed ovariectomized rats utilizing the push-pull perfusion technique [24].
  • Within the physiological range of brain glucose levels, leptin has a differential effect on VMN vs. ARC neurons, and acts on both glucosensing and non-glucosensing VMN neurons in a glucose-independent fashion with inhibition primarily dependent upon activation of the ATP-sensitive K+ channel [25].
  • We therefore hypothesized that a longer exposure time to high concentrations of progesterone might be required to mimic the leptin resistance that occurs on d 14 of pregnancy [26].

Physical interactions of Lep

  • Only when leptin was infused into the median eminence-arcuate nucleus complex was PRL secretion also stimulated, although its onset was 1 h behind that of LH [24].
  • Plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat [27].
  • These data indicate an extremely high turnover of leptin receptors in hypothalamic target sites, but also raise the possibility that leptin may interact with the Golgi apparatus-related mechanisms to alter intracellular mechanisms [28].
  • Megalin bound leptin in the presence of Ca(2+) and mediated its cellular internalization and degradation [29].
  • Leptin binding to its functional receptor leads to activation of the JAK-STAT-signaling pathway and especially to the activation of the signal transducer and activator of transcription factor 3 (STAT3) [30].

Enzymatic interactions of Lep

  • Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion [31].
  • Leptin increased mammalian target of rapamycin (mTor) that phosphorylates 4E-BP1 [32].
  • The effect of leptin is abolished when insulin secretion is induced with cAMP analogues that cannot be hydrolyzed by PDE3B [33].

Co-localisations of Lep


Regulatory relationships of Lep


Other interactions of Lep


Analytical, diagnostic and therapeutic context of Lep


  1. The stomach is a source of leptin. Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J.P., Bortoluzzi, M.N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., Lewin, M.J. Nature (1998) [Pubmed]
  2. Leptin action in the forebrain regulates the hindbrain response to satiety signals. Morton, G.J., Blevins, J.E., Williams, D.L., Niswender, K.D., Gelling, R.W., Rhodes, C.J., Baskin, D.G., Schwartz, M.W. J. Clin. Invest. (2005) [Pubmed]
  3. Leptin receptor-deficient obese Zucker rats reduce their food intake in response to a systemic supply of calories from glucose. Gilbert, M., Magnan, C., Turban, S., André, J., Guerre-Millo, M. Diabetes (2003) [Pubmed]
  4. The inhibitory effect of leptin on angiotensin II-induced vasoconstriction is blunted in spontaneously hypertensive rats. Rodríguez, A., Frühbeck, G., Gómez-Ambrosi, J., Catalán, V., Sáinz, N., Díez, J., Zalba, G., Fortuño, A. J. Hypertens. (2006) [Pubmed]
  5. Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells. Zachow, R.J., Magoffin, D.A. Endocrinology (1997) [Pubmed]
  6. Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. Delahaye, F., Breton, C., Risold, P.Y., Enache, M., Dutriez-Casteloot, I., Laborie, C., Lesage, J., Vieau, D. Endocrinology (2008) [Pubmed]
  7. Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Ahima, R.S., Kelly, J., Elmquist, J.K., Flier, J.S. Endocrinology (1999) [Pubmed]
  8. Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin. McMinn, J.E., Sindelar, D.K., Havel, P.J., Schwartz, M.W. Endocrinology (2000) [Pubmed]
  9. Leptin reduces food intake but does not alter weight regain following food deprivation in the rat. Velkoska, E., Morris, M.J., Burns, P., Weisinger, R.S. Int. J. Obes. Relat. Metab. Disord. (2003) [Pubmed]
  10. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Ainslie, D.A., Morris, M.J., Wittert, G., Turnbull, H., Proietto, J., Thorburn, A.W. Int. J. Obes. Relat. Metab. Disord. (2001) [Pubmed]
  11. Leptin: a potential novel antidepressant. Lu, X.Y., Kim, C.S., Frazer, A., Zhang, W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  12. Leptin-regulated endocannabinoids are involved in maintaining food intake. Di Marzo, V., Goparaju, S.K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G.I., Palmiter, R.D., Sugiura, T., Kunos, G. Nature (2001) [Pubmed]
  13. The effect of leptin on Lep expression is tissue-specific and nutritionally regulated. Wang, J., Liu, R., Liu, L., Chowdhury, R., Barzilai, N., Tan, J., Rossetti, L. Nat. Med. (1999) [Pubmed]
  14. High birth weight increases mammary tumorigenesis in rats. de Assis, S., Khan, G., Hilakivi-Clarke, L. Int. J. Cancer (2006) [Pubmed]
  15. Leptin induces nitric oxide synthase type II in C6 glioma cells. Role for nuclear factor-kappaB in hormone effect. Mattace Raso, G., Esposito, E., Iacono, A., Pacilio, M., Coppola, A., Bianco, G., Diano, S., Di Carlo, R., Meli, R. Neurosci. Lett. (2006) [Pubmed]
  16. Differential regulation of leptin synthesis in rats during short-term hypoxia and short-term carbon monoxide inhalation. Meissner, U., Hänisch, C., Ostreicher, I., Knerr, I., Hofbauer, K.H., Blum, W.F., Allabauer, I., Rascher, W., Dötsch, J. Endocrinology (2005) [Pubmed]
  17. Interaction between leptin and insulin signaling pathways differentially affects JAK-STAT and PI 3-kinase-mediated signaling in rat liver. Carvalheira, J.B., Ribeiro, E.B., Folli, F., Velloso, L.A., Saad, M.J. Biol. Chem. (2003) [Pubmed]
  18. Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced colitis in rats: role of capsaicin-sensitive vagal afferent fibers. Bozkurt, A., Cakir, B., Ercan, F., Yeğen, B.C. Regul. Pept. (2003) [Pubmed]
  19. Prevention of leptin binding to its receptor suppresses rat leukemic cell growth by inhibiting angiogenesis. Iversen, P.O., Drevon, C.A., Reseland, J.E. Blood (2002) [Pubmed]
  20. Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. Hâkansson, M.L., Brown, H., Ghilardi, N., Skoda, R.C., Meister, B. J. Neurosci. (1998) [Pubmed]
  21. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Elias, C.F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R.S., Bjorbaek, C., Flier, J.S., Saper, C.B., Elmquist, J.K. Neuron (1999) [Pubmed]
  22. Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. Wang, Q., Bing, C., Al-Barazanji, K., Mossakowaska, D.E., Wang, X.M., McBay, D.L., Neville, W.A., Taddayon, M., Pickavance, L., Dryden, S., Thomas, M.E., McHale, M.T., Gloyer, I.S., Wilson, S., Buckingham, R., Arch, J.R., Trayhurn, P., Williams, G. Diabetes (1997) [Pubmed]
  23. Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2. Anderwald, C., Müller, G., Koca, G., Fürnsinn, C., Waldhäusl, W., Roden, M. Mol. Endocrinol. (2002) [Pubmed]
  24. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. Watanobe, H. J. Physiol. (Lond.) (2002) [Pubmed]
  25. Effects of leptin on rat ventromedial hypothalamic neurons. Irani, B.G., Le Foll, C., Dunn-Meynell, A., Levin, B.E. Endocrinology (2008) [Pubmed]
  26. Induction of central leptin resistance in hyperphagic pseudopregnant rats by chronic prolactin infusion. Augustine, R.A., Grattan, D.R. Endocrinology (2008) [Pubmed]
  27. Plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat. Seeber, R.M., Smith, J.T., Waddell, B.J. Biol. Reprod. (2002) [Pubmed]
  28. Leptin receptor immunoreactivity is associated with the Golgi apparatus of hypothalamic neurons and glial cells. Diano, S., Kalra, S.P., Horvath, T.L. J. Neuroendocrinol. (1998) [Pubmed]
  29. Evidence indicating that renal tubular metabolism of leptin is mediated by megalin but not by the leptin receptors. Hama, H., Saito, A., Takeda, T., Tanuma, A., Xie, Y., Sato, K., Kazama, J.J., Gejyo, F. Endocrinology (2004) [Pubmed]
  30. Immunohistochemical evidence of functional leptin receptor expression in neuronal and endothelial cells of the rat brain. Mütze, J., Roth, J., Gerstberger, R., Matsumura, K., Hübschle, T. Neurosci. Lett. (2006) [Pubmed]
  31. Leptin signaling in the hypothalamus during chronic central leptin infusion. Pal, R., Sahu, A. Endocrinology (2003) [Pubmed]
  32. Effect of leptin on liver alcohol dehydrogenase. Mezey, E., Rennie-Tankersley, L., Potter, J.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  33. Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. Zhao, A.Z., Bornfeldt, K.E., Beavo, J.A. J. Clin. Invest. (1998) [Pubmed]
  34. Decreased leptin uptake in hypothalamic nuclei with ageing in Wistar rats. Fernández-Galaz, C., Fernández-Agulló, T., Campoy, F., Arribas, C., Gallardo, N., Andrés, A., Ros, M., Carrascosa, J.M. J. Endocrinol. (2001) [Pubmed]
  35. Leptin and connective tissue growth factor in advanced glycation end-product-induced effects in NRK-49F cells. Lee, C.I., Guh, J.Y., Chen, H.C., Lin, K.H., Yang, Y.L., Hung, W.C., Lai, Y.H., Chuang, L.Y. J. Cell. Biochem. (2004) [Pubmed]
  36. Leptin-mediated decrease of cyclin A2 and increase of cyclin D1 expression: relevance for the control of prepubertal rat Leydig cell division and differentiation. Fombonne, J., Charrier, C., Goddard, I., Moyse, E., Krantic, S. Endocrinology (2007) [Pubmed]
  37. Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: a novel circuit implicated in metabolic and endocrine regulations. Horvath, T.L., Diano, S., van den Pol, A.N. J. Neurosci. (1999) [Pubmed]
  38. Up-regulation of muscle UCP2 gene expression by a new beta3-adrenoceptor agonist, trecadrine, in obese (cafeteria) rodents, but down-regulation in lean animals. Berraondo, B., Marti, A., Duncan, J.S., Trayhurn, P., Martínez, J.A. Int. J. Obes. Relat. Metab. Disord. (2000) [Pubmed]
  39. Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats. Mitchell, S.E., Nogueiras, R., Rance, K., Rayner, D.V., Wood, S., Dieguez, C., Williams, L.M. J. Endocrinol. (2006) [Pubmed]
  40. Long-term effects of central leptin and resistin on body weight, insulin resistance, and beta-cell function and mass by the modulation of hypothalamic leptin and insulin signaling. Park, S., Hong, S.M., Sung, S.R., Jung, H.K. Endocrinology (2008) [Pubmed]
  41. Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats. Picó, C., Sánchez, J., Oliver, P., Palou, A. Obes. Res. (2002) [Pubmed]
  42. Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling. Morrison, C.D., Morton, G.J., Niswender, K.D., Gelling, R.W., Schwartz, M.W. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  43. Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Buyse, M., Ovesjö, M.L., Goïot, H., Guilmeau, S., Péranzi, G., Moizo, L., Walker, F., Lewin, M.J., Meister, B., Bado, A. Eur. J. Neurosci. (2001) [Pubmed]
  44. Evidence for a leptin-neuropeptide Y axis for the regulation of growth hormone secretion in the rat. Vuagnat, B.A., Pierroz, D.D., Lalaoui, M., Englaro, P., Pralong, F.P., Blum, W.F., Aubert, M.L. Neuroendocrinology (1998) [Pubmed]
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