Gastrointestinal hormones: Edited by Robert LowePeptide YYChandarana, Keval; Batterham, RachelAuthor Information Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London, WC1E 6JJ, UK Correspondence to Dr Rachel Batterham, University College London, UK Tel: +44 20 7679 0991; e-mail: [email protected] Current Opinion in Endocrinology, Diabetes and Obesity: February 2008 - Volume 15 - Issue 1 - p 65-72 doi: 10.1097/MED.0b013e3282f3f4b1 Buy Metrics Abstract Purpose of review This review discusses recent studies examining the effects of peptide YY on energy homeostasis, highlights the emerging hedonic effects of peptide YY and evaluates the therapeutic potential of the peptide YY system. Recent findings A role for exogenous PYY3-36 as an anorectic agent in obese humans and rodents has been established and weight loss effects demonstrated in obese rodents. New lines of evidence support a role for endogenous peptide YY in regulating energy homeostasis. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. Functional imaging in humans has confirmed that PYY3-36 activates brainstem and hypothalamic regions. The greatest effects, however, were observed within the orbitofrontal cortex, a brain region involved in reward processing. Further evidence for a hedonic role for PYY3-36 is supported by rodent studies showing that PYY3-36 decreases the motivation to seek high-fat food. Rodent studies using selective Y2 agonists and strategies combining PYY3-36/Y2 agonists with other anorectic agents have revealed increased anorectic and weight-reducing effects. Summary Peptide YY plays a role in the integrative regulation of metabolism. The emerging hedonic effects of peptide YY together with the weight-reducing effects observed in obese rodents suggest that targeting the peptide YY system may offer a therapeutic strategy for obesity. Copyright © 2008 Wolters Kluwer Health, Inc. All rights reserved.