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The role of oxyntomodulin and peptide tyrosine–tyrosine (PYY) in appetite control

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 612–620 (2006)Cite this article

Abstract

Oxyntomodulin and peptide tyrosine–tyrosine (PYY) are released from intestinal enteroendocrine cells in response to a meal. These circulating hormones are considered to be satiety signals, as they have been found to decrease food intake, body weight and adiposity in rodents. Their effect on energy homeostasis is mediated by the hypothalamus and brainstem, and several studies have demonstrated alterations in neuropeptide signaling within the arcuate nucleus. The weight loss that has been observed in animal models after repeated administration of oxyntomodulin and PYY has led to interest in developing these peptides as antiobesity therapies in humans. Indeed, preliminary studies have found that oxyntomodulin or PYY administration reduces food intake and body weight effectively in overweight human volunteers. This research suggests that modulation of these gut hormones could prove to be effective long-term therapies in the quest to combat the obesity epidemic.

Key Points

  • Oxyntomodulin and peptide tyrosine–tyrosine (PYY) are gut peptides that are released postprandially

  • Oxyntomodulin and PYY act as satiety signals via effects on appetite centers such as the hypothalamus and brainstem

  • Exogenous administration of oxyntomodulin or PYY3–36 reduces energy intake, adiposity and body weight in animals

  • Several studies suggest that drug therapy based on these hormones could be an effective treatment for human obesity

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Figure 1: Oxyntomodulin and PYY3–36 act as circulating satiety signals
Figure 2: The ARC of the hypothalamus receives and integrates circulating appetite signals

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Acknowledgements

The work on gastrointestinal peptides within the laboratory is funded by grants from the Wellcome Trust and Medical Research Council.

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Authors and Affiliations

  1. Wellcome Trust Clinical Research Fellow and Specialist Registrar in Endocrinology, Diabetes and Internal Medicine,

    Katie Wynne & Stephen R Bloom

  2. Department of Metabolic Medicine, Imperial College, London, UK

    Katie Wynne & Stephen R Bloom

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Correspondence to Stephen R Bloom.

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Competing interests

K Wynne declared she has no competing interests.

The use of oxyntomodulin for the treatment of obesity is the subject of two patent applications (WO 2003/022304 and WO 2004/06285) in the name of Imperial College Innovations, which are exclusively licensed to Thiakis Limited. SR Bloom is a Director of Thiakis Limited.

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Wynne, K., Bloom, S. The role of oxyntomodulin and peptide tyrosine–tyrosine (PYY) in appetite control. Nat Rev Endocrinol 2, 612–620 (2006). https://doi.org/10.1038/ncpendmet0318

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