Convergence of leptin and insulin signaling networks in obesity

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    Abstract

    Introduction Leptin (a 146 residue peptide) and insulin (a 30 amino acid dipeptide) are synthesized in distinct locations in the periphery but share a common function of long-term regulation of body weight and energy balance through direct alterations in hypothalamic arcuate nucleus (ARC) signaling (Sahu, 2004; Cone, 2005). Insulin is synthesized as a prohormone almost exclusively by pancreatic β-cells, and secreted into plasma in response to rising glucose levels. The mRNA for insulin has been found in some brain areas, suggesting that specific neurons may be capable of producing an ‘insulin-like’ peptide. Meanwhile leptin is synthesized and secreted mainly by adipocytes, and circulating levels are normally related to adiposity (Zhang <italic>et al</italic>., 1994; Frederich <italic>et al</italic>., 1995; Considine <italic>et al</italic>., 1996). There is some evidence that leptin is also produced by cells of the immune system such as T-cells and macrophages, bone, skeletal muscle, placenta, stomach, hypothalamus and by stellate cells of the liver. Direct administration of either hormone to the ARC has significant effects on feeding and body weight, while both hormones can cross the blood–brain barrier, probably via specific and saturable transport systems (Niswender & Schwartz, 2003; Niswender <italic>et al</italic>., 2004). Leptin and insulin stimulate proopiomelanocortin (POMC) expressing neurons in the ARC, resulting in processing of POMC to α-melanocyte-stimulating hormone (α-MSH) and subsequent activation of the melanocortin-3 and -4 receptors, leading to anorexigenic outputs.

    Original languageEnglish
    Title of host publicationNeurobiology of obesity
    EditorsJenni Harvey , Dominic J. Withers
    Place of PublicationCambridge
    PublisherCambridge University Press
    Pages127-163
    Number of pages37
    ISBN (Electronic)9780511541643
    ISBN (Print)9780521860338
    DOIs
    Publication statusPublished - 2008

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  • Cite this

    Sutherland, C., & Ashford, M. (2008). Convergence of leptin and insulin signaling networks in obesity. In J. Harvey , & D. J. Withers (Eds.), Neurobiology of obesity (pp. 127-163). Cambridge University Press. https://doi.org/10.1017/CBO9780511541643.006