The role of peptide YY in appetite regulation and obesity

• Published in: The Journal of physiology Vol. 587; no. 1; pp. 19 - 25
• Main Authors: Karra, Efthimia, Chandarana, Keval, Batterham, Rachel L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.01.2009; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Appetite Regulation - physiology; Eating - drug effects; Eating - physiology; Energy Metabolism - drug effects; Gastric Bypass; Humans; Obesity - drug therapy; Obesity - physiopathology; Obesity - surgery; Peptide Fragments; Peptide YY - administration & dosage; Peptide YY - physiology; Receptors, Gastrointestinal Hormone - drug effects; Receptors, Gastrointestinal Hormone - physiology; Symposium Section Reports: Orchestration of Metabolism in Health and Disease; Weight Loss - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2008.164269

The last decade has witnessed a marked increase in our understanding of the importance of gut hormones in the regulation of energy homeostasis. In particular, the discovery that the gut hormone peptide YY 3–36 (PYY3–36) reduced feeding in obese rodents and humans fuelled interest in the role of PYY3–36 in body weight regulation. Pharmacological and genetic approaches have revealed that the Y2-receptor mediates the anorectic effects of PYY3–36 whilst mechanistic studies in rodents identified the hypothalamus, vagus and brainstem regions as potential sites of action. More recently, using functional brain imaging techniques in humans, PYY3–36 was found to modulate neuronal activity within hypothalamic and brainstem, and brain regions involved in reward processing. Several lines of evidence suggest that low circulating PYY concentrations predispose towards the development and or maintenance of obesity. Subjects with reduced postprandial PYY release exhibit lower satiety and circulating PYY levels that correlate negatively with markers of adiposity. In addition, mice lacking PYY are hyperphagic and become obese. Conversely, chronic PYY3–36 administration to obese rodents reduces adiposity, and transgenic mice with increased circulating PYY are resistant to diet-induced obesity. Moreover, there is emerging evidence that PYY3–36 may partly mediate the reduced appetite and weight loss benefits observed post-gastric bypass surgery. Taken together these findings, coupled with the retained responsiveness of obese subjects to the effects of PYY3–36, suggest that targeting the PYY system may offer a therapeutic strategy to help treat obesity.