Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Leptin and Leptin Receptor

  • Lennart Zabeau
  • Frank Peelman
  • Jan TavernierEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101679


Leptin [LEP; Leptin; Leptin (murine obesity homolog); Leptin (obesity homolog, mouse); OB; Obese protein; Obese, mouse, homolog of; Obesity factor; OBS].

Leptin receptor [CD295; DB; HuB219; LEP-R; LEPR; Leptin receptor; OB receptor; OB-R; OBR].

Historical Background

People long believed that obesity is entirely behavioral (e.g., lack of willpower) and not physiological. This dogma was first challenged with the identification of two obese mouse strains. The ob/ob mouse had been discovered in 1950 and characterized as the first model for massive obesity, marked hyperphagia, and mild transient diabetes. In 1965, a new obesity mutant had been discovered: the db/db mouse. Besides the marked obesity and hyperphagia, and unlike the ob/obmutant, these animals develop severe, life-shortening diabetes. The phenotypes suggested that the genes are involved in a common metabolic pathway. When a wild type mouse was parabioticaly paired (surgically joining of the bloodstream of two...

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  1. Abel ED, Sweeney G. Modulation of the cardiovascular system by leptin. Biochimie. 2012;94:2097–103.  https://doi.org/10.1016/j.biochi.2012.03.019.CrossRefPubMedGoogle Scholar
  2. Balland E, Cowley MA. New insights in leptin resistance mechanisms in mice. Front Neuroendocrinol. 2015;39:59–65.  https://doi.org/10.1016/j.yfrne.2015.09.004.CrossRefPubMedGoogle Scholar
  3. Catteau A, Caillon H, Barrière P, Denis MG, Masson D, Fréour T. Leptin and its potential interest in assisted reproduction cycles. Hum Reprod Update. 2015;22.  https://doi.org/10.1093/humupd/dmv057.CrossRefPubMedGoogle Scholar
  4. Chen XX, Yang T. Roles of leptin in bone metabolism and bone diseases. J Bone Miner Metab. 2015;33:474–85.  https://doi.org/10.1007/s00774-014-0569-7.CrossRefPubMedGoogle Scholar
  5. Coleman DL. A historical perspective on leptin. Nat Med. 2010;16:1097–9.  https://doi.org/10.1038/nm1010-1097.CrossRefPubMedGoogle Scholar
  6. Farooqi IS, O’Rahilly S. 20 years of LEPTIN: human disorders of leptin action. J Endocrinol. 2014;223:T63–70.  https://doi.org/10.1530/JOE-14-0480.CrossRefPubMedGoogle Scholar
  7. García-Robles MJ, Segura-Ortega JE, Fafutis-Morris M. The biology of leptin and its implications in breast cancer: a general view. J Interf Cytokine Res. 2013;33(12):717–27.  https://doi.org/10.1089/jir.2012.0168.CrossRefGoogle Scholar
  8. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269:543–6.CrossRefPubMedGoogle Scholar
  9. Matarese G, Carrieri PB, Montella S, De Rosa V, La Cava A. Leptin as a metabolic link to multiple sclerosis. Nat Rev Neurol. 2010;6:455–61.  https://doi.org/10.1038/nrneurol.2010.89.CrossRefPubMedGoogle Scholar
  10. Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, Trayhurn P. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett. 1996;387:113–6.CrossRefPubMedGoogle Scholar
  11. Naylor C, Petri WA. Leptin regulation of immune responses. Trends Mol Med. 2016;22:88–98.  https://doi.org/10.1016/j.molmed.2015.12.001.CrossRefPubMedGoogle Scholar
  12. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and s. J Clin Endocrinol Metab. 1999;84:3686–95.CrossRefPubMedGoogle Scholar
  13. Park H-K, Ahima RS. Leptin signaling. F1000prime Reports. 2014;6:73.  https://doi.org/10.12703/P6-73.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Peelman F, Van Beneden K, Zabeau L, Iserentant H, Ulrichts P, Defeau D, Verhee A, Catteeuw D, Elewaut D, Tavernier J. Mapping of the leptin binding sites and design of a leptin antagonist. J Biol Chem. 2004;279:41038–46.  https://doi.org/10.1074/jbc.M404962200.CrossRefPubMedGoogle Scholar
  15. Reed AS, Unger EK, Olofsson LE, Piper ML, Myers MG, Xu AW. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes. 2010;59:894–906.  https://doi.org/10.2337/db09-1024.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263–71.  https://doi.org/10.1016/0092-8674(95)90151-5.CrossRefPubMedGoogle Scholar
  17. Vaisse C, Halaas JL, Horvath CM, Darnell JE, Stoffel M, Friedman JM. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet. 1996;14:95–7.  https://doi.org/10.1038/ng0996-95.CrossRefPubMedGoogle Scholar
  18. Wauman J, Tavernier J. Leptin receptor signaling: pathways to leptin resistance. Front Biosci. 2011;16:2771–93.  https://doi.org/10.2741/3885.CrossRefGoogle Scholar
  19. Zabeau L, Peelman F, Tavernier J. Leptin: from structural insights to the design of antagonists. Life Sci. 2015.  https://doi.org/10.1016/j.lfs.2015.04.015.CrossRefPubMedGoogle Scholar
  20. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.  https://doi.org/10.1038/372425a0.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Medical Biotechnology Center, Faculty of Medicine and Health SciencesFlanders Institute for Biotechnology, Ghent UniversityGhentBelgium