Effect of Peptide YY3-36 on Food Intake in Humans

Background & Aims: Studies in animals and humans suggest a role for peptide YY (PYY3-36) in regulating satiety. The physiologic role of PYY3-36, however, has not been investigated in detail. Methods: The present study was designed to examine PYY release in response to 2 meals differing in their calorie content and to relate the plasma levels to those obtained after exogenous infusion. In a second step, the effect of graded intravenous doses (0, 0.2, 0.4, and 0.8 pmol · kg−1 · min−1) of synthetic human PYY3-36 on food intake was investigated in healthy male volunteers in a double-blind, placebo-controlled fashion. Results: Plasma PYY concentrations increased in response to food intake reflecting the size of the calorie load. Graded PYY3-36 infusions resulted in a dose-dependent reduction in food intake (maximal inhibition, 35%; P < .001 vs control) and a similar reduction in calorie intake (32%; P < .001). Fluid ingestion was also reduced by PYY (18% reduction; P < .01). Nausea and fullness were the most common side effects produced by PYY, especially at the highest dose. Furthermore, subjects experienced less hunger and early fullness in the premeal period during PYY3-36 infusion at the highest dose (P < .05). Conclusions: This study shows that intravenous infusions of PYY3-36 decrease spontaneous food intake; the inhibition is, however, only significant at pharmacologic plasma concentrations. Whether PYY3-36 has a physiologic role in the regulation of satiety in humans remains to be defined.