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Peripheral satiety signals: view from the Chair

International Journal of Obesity volume 33, pages S3–S6 (2009)Cite this article

The discovery and characterization of peripheral signals that regulate food intake and energy balance dates back over 50 years. Beginning with the ‘glucostatic’ and ‘lipostatic’ hypotheses, nutrients were considered strong candidates that could ‘tell’ the brain the state of satiety (glucose) or overall energy stores (fat), so that food intake and energy expenditure could be regulated to maintain energy balance.1, 2 Both of these hypotheses endure to this day. The lipostatic hypothesis remains as a central concept in our understanding of the regulation of energy balance. This is based on the key observations that (a) insulin is secreted from the pancreas in direct proportion to fat stores and provides a signal to the brain to initiate long-term changes in energy expenditure and food intake3 and (b) the peptide hormone leptin is released from adipose tissue itself, and defects in either the production or the signalling of leptin lead to obesity.4 The glucostatic hypothesis received validation with the discovery of glucose-sensitive neurons in the hypothalamic regions involved in the control of energy balance.5, 6

Over the years, other nutrient-based hypotheses were developed and the existing ones were modified, but none of these were completely capable of explaining the short-term control of food intake or certain aspects of long-term energy balance. In the early 1970s, Gibbs et al.7 found a gastrointestinal hormone, cholecystokinin (CCK), that produced satiety in rats. This discovery heralded the era of the ‘gut hormones’ as regulators of both food intake and energy balance. We now recognize more than 20 gut-derived peptides and lipid mediators are involved in aspects of energy homeostasis.8, 9, 10 Many of these have now been tested or developed as potential therapeutic agents for the treatment of metabolic disorders or to aid in weight management. It seems unlikely that the full complement of peripheral energy balance signals have been discovered. As more are found, the opportunities for the development of novel therapeutics must be balanced with challenges of understanding their role in the physiology and pathophysiology of this complex regulatory system. Major challenges remain: How do the plethora of peripheral signals get integrated in the brain? Similarly, how does the brain actually receive these signals in the first place? In the three articles following this viewpoint, Timothy Moran,11 Harvey Grill,12 and Alastair Ferguson13 and their colleagues begin to address these challenges by outlining where signals released from the gut and adipose tissues act to regulate energy balance.

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Acknowledgements

I thank Adam Chambers for valuable comments on the manuscript. KA Sharkey is an Alberta Heritage Foundation for Medical Research Medical Scientist and the Crohn's and Colitis Foundation of Canada Chair in Inflammatory Bowel Disease Research at the University of Calgary.

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  1. Department of Physiology & Biophysics, Hotchkiss Brain Institute and Snyder Institute of Infection, Inflammation and Immunity, University of Calgary, Calgary, Alberta, Canada

    K A Sharkey

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Correspondence to K A Sharkey.

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Sharkey, K. Peripheral satiety signals: view from the Chair. Int J Obes 33 (Suppl 1), S3–S6 (2009). https://doi.org/10.1038/ijo.2009.8

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