NIA0003 The role of peptide YY (PYY) in the control of appetite

Abstract

Peptide YY (PYY) is a 36 amino acid gut hormone produced by the distal intestinal tract that binds the Y2 receptor in the hypothalamic arcuate nucleus. We showed that increasing calorie load in normal weight humans and rodents causes a graded rise in endogenous PYY (P < 0.05). Graded doses of exogenous PYY showed a dose response curve for increased satiety (P < 0.05) and reduced calorie intake (P < 0.05). This study demonstrated two threshold levels, the lower marking the start of appetite reduction (P = 0.04) and the upper the onset of nausea (P = 0.03). We subsequently showed that obese humans and rodents have lower postprandial PYY responses (P < 0.05). Reduced plasma PYY was characterized by normal PYY mRNA levels and higher tissue PYY levels, indicating normal production, but attenuated release from the distal gut. However in obese humans and rodent exogenous PYY was still effective at increasing satiety and reducing food intake (P < 0.05). Rodents following gastric bypass showed elevated PYY, reduced food intake and gut hypertrophy (P = 0.01), while blockade of endogenous PYY increased food intake (P = 0.04). In man, gastric bypass, but not gastric banding caused increased postprandial PYY favouring enhanced satiety (P = 0.001). Our prospective human gastric bypass study showed progressively increasing PYY responses associated with enhanced satiety (P < 0.05). The sustained nature of appetite reduction after gastric bypass may partly be explained by gut adaptation and chronic elevation of PYY. Thus obesity is associated with low PYY release that reduces satiety and reinforces obesity. The maladaptive reduction in PYY release can however be overcome by gastric bypass.