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.
Chelikani
Prasanth K
PK
Department of Veterans Affairs-Nebraska Western Iowa Health Care System (151), 4101 Woolworth Avenue, Omaha, Nebraska 68105, USA.
Haver
Alvin C
AC
Reidelberger
Roger D
RD
D000818:Animals; D019422:Dietary Sucrose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D004750:Enteral Nutrition; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019422:Dietary Sucrose; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)