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Submitted on August 26, 2004
Accepted on November 5, 2004
Department of Veterans Affairs - Nebraska Western Iowa Health Care System, Omaha, Nebraska 68105 and Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178
* To whom correspondence should be addressed. E-mail: roger.reidelberger{at}med.va.gov.
Prasanth K. Chelikani, Alvin C. Haver, and Roger D. Reidelberger. Intravenous infusion of PYY (3-36) potently inhibits food intake in rats. 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 intravenous infusions of PYY (3-36) and PYY (1-36) (0.5 to 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 % 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 to 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) intravenous infusions of PYY (3-36), which are more likely than intraperitoneal 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 intravenous doses of PYY (3-36) that reproduce postprandial increases in plasma PYY (3-36) are sufficient to inhibit food intake.
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