Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

  • Hyeong-Kyu Park
    Affiliations
    Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
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  • Rexford S. Ahima
    Correspondence
    Corresponding author at: Division of Endocrinology, Diabetes and Metabolism, and the Institute for Diabetes, Obesity and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 12–104 Translational Research Center, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
    Affiliations
    Division of Endocrinology, Diabetes and Metabolism, and the Institute for Diabetes, Obesity and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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      Abstract

      Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases.

      Abbreviations:

      ACC (acetyl-CoA carboxylase), AgRP (agouti-related peptide), AMPK (AMP-activated protein kinase), ARC (arcuate nucleus), BAT (brown adipose tissue), CART (cocaine- and amphetamine-regulated transcript), CCK (cholecystokinin), CNS (central nervous system), FGF (fibroblast growth factor), FoxO1 (Forkhead box O1), GH (growth hormone), GLP-1 (glucagon-like peptide 1), GnRH (gonadotropin-releasing hormone), IGF (insulin-like growth factor), IGFBP (IGF binding factor), IL (interleukin), IRS (insulin receptor substrate), JAK2 (Janus kinase 2), LH (luteinizing hormone), LHA (lateral hypothalamic area), MAPK (mitogen-activated protein kinase), MCH (melanin-concentrating hormone), NPY (neuropeptide Y), NTS (nucleus of the solitary tract), LepR (leptin receptor), LepRb (long isoform of leptin receptor), PI3K (phosphatidylinositol 3-kinase), POMC (pro-opiomelanocortin), PTP1B (protein tyrosine phosphatase 1B), PYY (peptide YY), SF-1 (steroidogenic factor 1), SHP2 (SH2-containing protein tyrosine phosphatase 2), SOCS3 (suppressor of cytokine signaling 3), STAT3 (signal transducer and activator of transcription 3), T3 (tri-iodothyronine), T4 (thyroxine), TNF (tumor necrosis factor), TRH (thyrotropin-releasing hormone), TSH (thyroid stimulating hormone), UCP (uncoupling protein), VMH (ventromedial hypothalamus), VTA (ventral tegmental area), WAT (white adipose tissue)

      Keywords

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