Peptide YY

Also known as: PYY-I, Peptide tyrosine tyrosine, PYY, P10082

Peptide YY (PYY) is a 36-amino acid gut hormone primarily secreted by L-cells in the distal gastrointestinal tract in response to caloric intake. Its mechanism of action involves binding to neuropeptide Y receptors, specifically Y1 and Y2 subtypes, which are expressed in the central nervous system and peripheral tissues. Activation of Y2 receptors in the hypothalamus, particularly in the arcuate nucleus, mediates anorexigenic signaling by inhibiting orexigenic neurons (e.g., NPY/AgRP), thereby reducing appetite and food intake. PYY also delays gastric emptying and modulates intestinal motility via Y1 receptor interactions. Key research findings indicate that circulating PYY levels rise postprandially, with the truncated form PYY(3-36) being the predominant active isoform. Studies in animal models and humans demonstrate that exogenous PYY(3-36) administration significantly decreases caloric intake and body weight, with effects lasting several hours. Additionally, PYY has been implicated in energy homeostasis, glucose metabolism, and gut-brain communication. Over 3,100 PubMed references support its role in obesity, metabolic syndrome, and eating disorders, though variability in individual responses and potential nausea side effects have been noted. Clinically, PYY analogs are under investigation as potential anti-obesity therapeutics, with some progressing to early-phase trials. However, no PYY-based drugs are currently approved for clinical use. Its relevance extends to understanding post-bariatric surgery weight loss, where elevated PYY levels are observed. Further research is needed to optimize dosing, minimize adverse effects, and explore combinatorial therapies with other gut hormones (e.g., GLP-1). For research purposes only — not medical advice.

Key data

Mechanism of action

Ligand for neuropeptide Y receptor type 1 (NPY1R) and neuropeptide Y receptor type 2 (NPY2R) (PubMed:1317848, PubMed:7592910, PubMed:36525977). Also binds NPY5R (By similarity). Receptor binding induces adenylate cyclase-inhibiting G protein-coupled receptor signaling, resulting in inhibition of cAMP production (PubMed:1317848, PubMed:7592910). Receptor activation by PYY also leads to an increase of intracellular Ca(2+) levels (PubMed:1317848, PubMed:36525977, PubMed:7592910). This gut peptide inhibits exocrine pancreatic secretion (By similarity). Involved in the regulation of colonic antisecretory tone, and colonic contractility (By similarity)

Research & studies

Frequently asked questions

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