PYY

Peptide YY (PYY) is a peptide hormone produced by enteroendocrine L cells in the distal small intestine (ileum) and colon. It is released into the bloodstream after a meal, with postprandial levels rising in response to caloric intake, especially fats and proteins. PYY acts as part of the gut–brain axis to regulate appetite and energy balance.

Biochemistry and forms: PYY is synthesized as a larger precursor and processed into active forms, notably PYY1-36 and the truncated PYY3-36. The circulating form PYY3-36 is abundant and is considered a principal mediator of meal-induced satiety in humans.

Receptors and mechanism: PYY interacts with neuropeptide Y (NPY) receptors, including Y1, Y2, and Y5 subtypes. PYY3-36 has relatively higher affinity for Y2 receptors and is thought to suppress appetite largely by inhibiting NPY signaling in the hypothalamus, particularly in the arcuate nucleus. In addition to appetite regulation, PYY can slow gastric emptying and influence gut motility through other receptor interactions, contributing to feelings of fullness after eating.

Physiological role and clinical relevance: PYY participates in short-term regulation of energy intake and meal termination. Experimental administration of PYY or PYY3-36 reduces hunger and reduces food intake in humans, but effects on long-term weight loss are variable, and trials have not established a robust therapeutic benefit. Side effects reported in studies can include nausea and abdominal discomfort. PYY-related therapies are not currently approved; research continues into obesity and metabolic disorders.

Genetics and regulation: PYY is encoded by the PYY gene and is predominantly expressed in intestinal L cells. Secretion is stimulated by nutrient intake and other factors related to feeding and energy status.