Peptide YY (PYY)

Endogenous Hormone

Peptide YY (PYY) is a 36-amino-acid hormone released by enteroendocrine L-cells in the lining of the lower small intestine (ileum) and colon. It is one of the body's principal satiety signals: levels rise after eating — roughly in proportion to the calories and especially the fat and protein consumed — and help tell the brain that a meal has been sufficient. Because PYY is a hormone the body produces itself, it is not sold or used as a drug, and this page is an educational reference to its biology, which underpins several anti-obesity and metabolic drug strategies. PYY circulates in two main forms. The full-length peptide (PYY1-36) is cleaved by the enzyme dipeptidyl peptidase-4 (DPP-4) to produce PYY3-36, the shorter active form responsible for most of its appetite-suppressing effects. PYY3-36 acts as a relatively selective agonist of the Y2 receptor, a member of the neuropeptide Y receptor family. By engaging Y2 receptors in the hypothalamus and on vagal pathways, PYY3-36 dampens the activity of hunger-promoting NPY/AgRP neurons and reduces food intake — placing it in direct functional contrast to its relative neuropeptide Y (NPY), which stimulates appetite. PYY sits at the heart of the gut–brain axis and has become especially interesting because of two observations. First, PYY levels are markedly elevated after bariatric (metabolic) surgery, and this rise is thought to contribute to the reduced appetite and durable weight loss that follow procedures like gastric bypass and sleeve gastrectomy. Second, this natural satiety biology has made PYY3-36 an attractive template for drug development — particularly as a component of combination or co-agonist therapies alongside GLP-1-based agents. The goal is to recreate, pharmacologically, the multi-hormone satiety environment that surgery produces. Because it is a satiety hormone, PYY is closely linked to the other appetite-regulating peptides on this site. It belongs to the same PP-fold family as neuropeptide Y and pancreatic polypeptide, complements the incretin hormone pathways targeted by semaglutide and tirzepatide, and works alongside amylin biology represented by pramlintide. It is also conceptually related to oxyntomodulin, another L-cell product that reduces appetite. For background, see our overviews of satiety hormones, appetite control, and the use-case discussion of PYY and satiety.