hormonesPYY

Peptide YY (PYY) is a gut-derived peptide hormone in the neuropeptide Y family. It is produced by enteroendocrine L cells in the distal small intestine and colon and released into the bloodstream after a meal, with higher levels following meals rich in fat and protein.

PYY is synthesized as a larger precursor called prepro-PYY and is processed to the circulating forms PYY1-36 and, after enzymatic truncation by dipeptidyl peptidase IV, PYY3-36. PYY3-36 is the major circulating form detected after meals and is considered the primary active form in appetite regulation.

The primary action of PYY is to reduce appetite and food intake. It largely operates through Y receptor signaling, especially the Y2 receptor on hypothalamic neurons, where it inhibits NPY/AgRP neurons, dampening orexigenic signals. PYY also slows gastric emptying and intestinal transit, contributing to feelings of fullness.

Physiological and clinical relevance has focused on postprandial PYY dynamics and body weight. Post-meal PYY levels rise in humans, but the magnitude of this response can vary with macronutrient content and body habitus. In obesity, some studies report blunted postprandial PYY responses, though findings are not entirely consistent. Because of its role in appetite regulation, PYY and its analogues have been explored as potential anti-obesity therapies, but clinical development has faced challenges related to efficacy and tolerability.

PYY interacts with other gut hormones, such as GLP-1, within the complex network that controls energy intake.