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20 years of leptin: From the discovery of the leptin gene to leptin in our therapeutic armamentarium

Published:October 28, 2014DOI:https://doi.org/10.1016/j.metabol.2014.10.023
      This issue of the journal Metabolism celebrates the 20 years since the discovery of the prototypical adipose tissue secreted hormone leptin [
      • Ingalls A.M.
      • Dickie M.M.
      • Snell G.D.
      Obese, a new mutation in the house mouse.
      ,
      • Zhang Y.
      • Proenca R.
      • Maffei M.
      • Barone M.
      • Leopold L.
      • Friedman J.M.
      Positional cloning of the mouse obese gene and its human homologue.
      ,
      • Moon B.C.
      • Friedman J.M.
      The molecular basis of the obese mutation in ob2j mice.
      ,
      • Coleman D.L.
      Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice.
      ,
      • Hervey G.R.
      Regulation of energy balance.
      ,
      • Friedman J.M.
      • Halaas J.L.
      Leptin and the regulation of body weight in mammals.
      ,
      • Halaas J.L.
      • Gajiwala K.S.
      • Maffei M.
      • Cohen S.L.
      • Chait B.T.
      • Rabinowitz D.
      • Lallone R.L.
      • Burley S.K.
      • Friedman J.M.
      Weight-reducing effects of the plasma protein encoded by the obese gene.
      ,
      • Lee G.H.
      • Proenca R.
      • Montez J.M.
      • Carroll K.M.
      • Darvishzadeh J.G.
      • Lee J.I.
      • Friedman J.M.
      Abnormal splicing of the leptin receptor in diabetic mice.
      ,
      • 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.
      Identification and expression cloning of a leptin receptor, OB-R.
      ]. Leptin has proven to be a key marker of the amount of energy stores in the body, and leptin levels circulate at levels proportional to the amount of the amount of body fat, signaling available energy stores [
      • Maffei M.
      • Halaas J.
      • Ravussin E.
      • Pratley R.E.
      • Lee G.H.
      • Zhang Y.
      • Fei H.
      • Kim S.
      • Lallone R.
      • Ranganathan S.
      • et al.
      Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.
      ]. Leptin levels also decrease in response to acute caloric deprivation, suggesting a role for leptin in the broader context of regulating energy homeostasis [
      • Chan J.L.
      • Heist K.
      • DePaoli A.M.
      • Veldhuis J.D.
      • Mantzoros C.S.
      The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men.
      ]. In the spirit of science, leptin has proven to be unpredictable and truly fascinating—a system worth exploring and understanding. Indeed, the discovery of leptin has changed our understanding of adipose tissue and energy regulation and has provided a much better understanding of the connection between energy reserves and several physiological functions including but not limited to metabolism, reproductive function and immune function. At this twentieth anniversary of its discovery, papers to be published in this special issue on leptin present the wealth of knowledge that has been gained in this field and also highlight the many questions that remain to be answered.
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