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5 - Convergence of leptin and insulin signaling networks in obesity

Published online by Cambridge University Press:  15 September 2009

By
Calum Sutherland  and
Mike Ashford
Edited by
Jenni Harvey  and
Dominic J. Withers
Calum Sutherland
Affiliation:
Division of Pathology and Neurosciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
Mike Ashford
Affiliation:
Division of Pathology and Neurosciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY UK
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
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Summary

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 et al., 1994; Frederich et al., 1995; Considine et al., 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 et al., 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.

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Neurobiology of Obesity , pp. 127 - 163
Publisher: Cambridge University Press
Print publication year: 2008

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