Peptide YY (PYY) is a 36-amino-acid gut hormone released by L-cells in the ileum and colon following meals. PYY3-36, the predominant circulating form, acts on Y2 receptors in the hypothalamic arcuate nucleus to suppress appetite. It is one of the best-characterized satiety hormones, with human infusion studies consistently showing 30% reduction in caloric intake. Obese individuals have lower postprandial PYY levels, making it a rational therapeutic target, though clinical development has been complicated by nausea at effective doses.
Category: Satiety / Metabolic. Evidence rating: B (meaningful human data).
Clinical status: Well-characterized endogenous hormone. Infusion studies in humans completed. No approved PYY-based drug.
PYY3-36 crosses the blood-brain barrier and binds to inhibitory Y2 receptors on orexigenic NPY/AgRP neurons in the arcuate nucleus, reducing their activity and thereby suppressing appetite. It also activates anorexigenic POMC neurons. Peripherally, PYY slows gastric emptying ("ileal brake"…
Safety considerations: Human infusion studies show dose-dependent nausea as the primary limiting side effect; IV PYY3-36 is well-tolerated at lower doses in controlled clinical studies; No serious adverse events reported in human infusion studies.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~4050 g/mol (PYY3-36) |
|---|---|
| Half-life | ~7 minutes (rapid DPP-IV degradation) |
| Production method | bioactive |
| Anti-doping status | not-listed |
| US regulatory status | Not FDA-approved as a therapeutic. Research use only. Endogenous hormone. |
Despite robust human data showing 30% caloric reduction, PYY-based drugs have not succeeded clinically. Nausea at effective doses, short half-life requiring infusion, and the success of GLP-1 agonists have diverted pharmaceutical investment away from PYY monotherapy.
PYY and GLP-1 are both released by L-cells and have complementary appetite-suppressing mechanisms. Some researchers believe the full benefit of GLP-1 agonists includes increased PYY release. Combination approaches are being explored.
Yes. PYY release is stimulated by dietary protein and fiber, exercise, and adequate caloric intake. High-protein meals produce the largest PYY response. Caloric restriction paradoxically reduces PYY.
No, though they are related. PYY and NPY belong to the same peptide family and share receptor affinity, but they have opposing effects on appetite: NPY is orexigenic (appetite-stimulating) while PYY3-36 is anorexigenic (appetite-suppressing).