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4 - Leptin and insulin as adiposity signals

Published online by Cambridge University Press:  15 September 2009

By
Kevin D. Niswender
Edited by
Jenni Harvey  and
Dominic J. Withers
Kevin D. Niswender
Affiliation:
Diabetes, Endocrinology and Metabolism, 715, Preston Research Building, Vanderbilt University, Medical Center, 2220, Pierce Avenue Nashville, TN 37232–6303, USA
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
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Summary

Summary

Obesity is an epidemic in the USA and worldwide. Despite a rapid increase in the burden of obesity, scientific evidence indicates that body adiposity is a tightly regulated physiological variable. Current models implicate a classical endocrine feedback loop in the process termed energy homeostasis. Both the pancreatic β cell-derived hormone insulin and the adipocyte-derived hormone leptin are secreted in proportion to fat mass and, thus, signal the status of body energy stores to the hypothalamus. Key hypothalamic nuclei contain neurons that respond directly to insulin and leptin and integrate these and other signals in order to regulate food intake and energy homeostasis through a series of complex neuronal circuits.

Although the personal, societal and economic costs of obesity are staggering, the medical research community has yet to develop definitive therapies. Recent advances in our understanding of the interactions of insulin and leptin with hypothalamic target neurons has shed light upon potential pathophysiological mechanisms and therefore therapeutic targets. In this chapter, basic mechanisms of energy homeostasis will be presented in the context of an adiposity negative feedback model with the hormones insulin and leptin serving an important role. This model will then be extended and discussed in the context of the pathophysiology of obesity.

Introduction

Obesity is an international health epidemic (Kopelman, 2000; Mokdad et al., 2001) afflicting 1.7 billion people worldwide (James, 2003) and has surpassed infectious disease and under-nutrition as the major threat to health in most parts of the world.

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Neurobiology of Obesity , pp. 83 - 126
Publisher: Cambridge University Press
Print publication year: 2008

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  • Leptin and insulin as adiposity signals
    • By Kevin D. Niswender, Diabetes, Endocrinology and Metabolism, 715, Preston Research Building, Vanderbilt University, Medical Center, 2220, Pierce Avenue Nashville, TN 37232–6303, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.005
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  • Leptin and insulin as adiposity signals
    • By Kevin D. Niswender, Diabetes, Endocrinology and Metabolism, 715, Preston Research Building, Vanderbilt University, Medical Center, 2220, Pierce Avenue Nashville, TN 37232–6303, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.005
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  • Leptin and insulin as adiposity signals
    • By Kevin D. Niswender, Diabetes, Endocrinology and Metabolism, 715, Preston Research Building, Vanderbilt University, Medical Center, 2220, Pierce Avenue Nashville, TN 37232–6303, USA
  • Edited by Jenni Harvey, University of Dundee, Dominic J. Withers, Imperial College of Science, Technology and Medicine, London
  • Book: Neurobiology of Obesity
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541643.005
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