Peptide YY (PYY)
A 36 amino acid gut hormone released from intestinal L-cells after eating that suppresses appetite and slows gastric emptying. PYY acts alongside GLP-1 as part of the gut's satiety signalling system. Understanding PYY biology provides context for the appetite-suppressing mechanisms of GLP-1 receptor agonists.
Technical Context
PYY is released from intestinal L-cells (the same cells that produce GLP-1) in proportion to caloric intake. PYY(3-36) (the DPP-4 cleaved form, which is the major circulating species) acts on Y2 receptors in the hypothalamic arcuate nucleus to suppress appetite by inhibiting NPY/AgRP neurons and activating POMC neurons. PYY also slows gastric emptying and intestinal transit (the ileal brake mechanism). GLP-1 and PYY are co-secreted and have synergistic appetite-suppressing effects. GLP-1 RA treatment may increase endogenous PYY secretion, potentially contributing to appetite suppression beyond direct GLP-1R activation. PYY analogues have been explored as potential obesity therapeutics but have not reached approval.