Peptide YY 3-36 (PYY3-36) is produced by the gut and is released into the circulation in response to food ingestion. Peripheral administration of PYY3-36 leads to a marked inhibition of food intake. PYY3-36 acts on the arcuate nucleus to inhibit release of the appetite stimulating hormone NPY and stimulates release of αMSH.

In humans, food intake is reduced by 30% following intravenous infusion of PYY3-36 at plasma levels similar to those achieved physiologically after a meal. Obese subjects have lower basal fasting PYY3-36 levels and have a smaller rise in post-prandial levels. Obesity does not appear to be associated with resistance to PYY3-36, as infusion of PYY3-36 resulted in a reduction in food intake by 30% in an obese group compared to 31% in a lean control group.

In addition, endogenous levels of PYY3-36 were found to be lower in obese subjects, with the increase in circulating PYY3-36 associated with food intake resulting only in a plasma level near equivalent to the basal, pre-prandial level of PYY3-36 in lean subjects. Thus a functional PYY3-36 deficiency may be an important component of the pathogenesis of obesity.