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Bowels control brain: gut hormones and obesity

Abstract

Food intake and energy expenditure are tightly regulated by the brain, in a homeostatic process that integrates diverse hormonal, neuronal and metabolic signals. The gastrointestinal tract is an important source of such signals, which include several hormones released by specialized enteroendocrine cells. These hormones exert powerful effects on appetite and energy expenditure. This Review addresses the physiological roles of peptide YY, pancreatic polypeptide, islet amyloid polypeptide, glucagon-like peptide 1, glucagon, oxyntomodulin, cholecystokinin and ghrelin and discusses their potential as targets for the development of novel treatments for obesity.

Key Points

  • The history of pharmacological therapies for obesity is characterized principally by inefficacy and marked adverse effects

  • Robust weight loss can be achieved through bariatric surgery, with associated changes in the intestinal hormonal response to calorie intake

  • Gut hormones such as glucagon-like peptide 1, peptide YY, pancreatic polypeptide, glucagon and islet amyloid polypeptide act in an integrated fashion to modulate appetite and energy expenditure

  • A potential therapy for obesity might be based on the concept of pharmacological mimicry of the hormonal milieu after bariatric surgery

  • Development of such therapies will, however, require improved understanding of the interactions between hormones and of their integration with other signals of nutritional status

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Figure 1: A complex neuronal network within the CNS controls energy homeostasis.
Figure 2: Comparison of bariatric surgical procedures.
Figure 3: Tissue-specific proglucagon cleavage.

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Correspondence to Stephen R. Bloom.

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S. R. Bloom declares an association with the following company: Wyeth Pharmaceuticals. S. R. Bloom is the inventor of patents describing the use of gut hormones and their analogs and derivatives in the treatment of obesity, and is a consultant for Thiakis, a subsidiary of Wyeth Pharmaceuticals. The other authors declare no competing interests.

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Field, B., Chaudhri, O. & Bloom, S. Bowels control brain: gut hormones and obesity. Nat Rev Endocrinol 6, 444–453 (2010). https://doi.org/10.1038/nrendo.2010.93

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