Protein and Peptide YY

Cell Metabolism, Vol 4, 223-233, September 2006

Critical role for peptide YY in protein-mediated satiation and body-weight regulation

Rachel L. Batterham,1, Helen Heffron,1 Saloni Kapoor,1 Joanna E. Chivers,1 Keval Chandarana,1 Herbert Herzog,2 Carel W. Le Roux,3 E. Louise Thomas,4 Jimmy D. Bell,4 and Dominic J. Withers1

1 Centre for Diabetes and Endocrinology, Department of Medicine, University College London, WC1E 6JJ, United Kingdom
2 The Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
3 Department of Metabolic Medicine, Hammersmith Hospital, Imperial College, Du Cane Road, London, W12 0NN, United Kingdom
4 Molecular Imaging Group, Imaging Sciences Department, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, W12 0NN, United Kingdom

Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity.