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Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects

Published online by Cambridge University Press:  09 March 2007

Per M. Hellström ,
Allan Geliebter ,
Erik Näslund ,
Peter T. Schmidt ,
Eric K. Yahav ,
Sami A. Hashim  and
Martin R. Yeomans
Per M. Hellström
Affiliation:
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
Allan Geliebter
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Erik Näslund
Affiliation:
Division of Surgery, Karolinska Institutet Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
Peter T. Schmidt
Affiliation:
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
Eric K. Yahav
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Sami A. Hashim
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Martin R. Yeomans*
Affiliation:
Department of Psychology, School of Life Sciences, University of Sussex, Brighton, Sussex BN1 9QG, UK
*
*Corresponding author: Dr Martin R. Yeomans, fax +44 1273 678058, email martin@sussex.ac.uk
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Abstract

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The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and α-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

Keywords

Signalling systemsObesityHormones
Type
Research Article
Information
British Journal of Nutrition , Volume 92 , Issue S1 , August 2004 , pp. S47 - S57
Copyright
Copyright © The Nutrition Society 2004

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