Intravenous Infusion of Peptide YY(3–36) Potently Inhibits Food Intake in Rats

Peptide YY (3–36) [PYY (3–36)] is postulated to act as a hormonal signal from the gut to the brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a prolonged 2–3 h increase in plasma levels of both PYY (3–36) and PYY (1–36). We determined the dose-dependent effects of 3-h iv infusions of PYY (3–36) and PYY (1–36) (0.5–50 pmol·kg−1·min−1) at dark onset on food intake in non-food-deprived rats. PYY (3–36) dose-dependently inhibited food intake: the minimal effective dose was 5 pmol·kg−1·min−1; the estimated potency (mean effective dose) and efficacy (maximal percent inhibition) were 15 pmol·kg−1·min−1 (2.6 nmol/kg) and 47%, respectively. PYY (1–36) was an order of magnitude less potent than PYY (3–36). Similar total doses of PYY (3–36) (0.9–30 nmol/kg) infused during the 15-min period just before dark onset also dose-dependently inhibited food intake, albeit with a lower potency and efficacy. Other experiments showed that PYY (3–36) inhibited food intake in sham-feeding rats and was more effective in reducing intake of a mixed-nutrient liquid diet than 15% aqueous sucrose. We conclude that: 1) iv infusions of PYY (3–36), which are more likely than ip injections to mimic postprandial increases in plasma PYY (3–36), potently inhibit food intake in a dose-dependent manner; 2) PYY (1–36) is an order of magnitude less potent than PYY (3–36); and 3) PYY (3–36) can inhibit food intake independently of its action to inhibit gastric emptying. It remains to be determined whether iv doses of PYY (3–36) that reproduce postprandial increases in plasma PYY (3–36) are sufficient to inhibit food intake.