Ghrelin Attenuates the Inhibitory Effects of Glucagon-Like Peptide-1 and Peptide YY(3-36) on Food Intake and Gastric Emptying in Rats

Abstract

Ghrelin stimulates, while glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) [PYY(3-36)] inhibit, food intake and gastric emptying in rats. We determined the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake in freely feeding rats, and on the inhibitory effects of intravenous infusion of GLP-1 and PYY(3-36) on food intake and gastric emptying. Ghrelin (150 pmol x kg(-1) x min(-1)) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol x kg(-1) x min(-1) had no effect. GLP-1 (15 pmol x kg(-1) x min(-1)) inhibited food intake by 35-54%; coinfusion of ghrelin at 50 and 150 pmol x kg(-1) x min(-1) attenuated this effect by 60 and 64%, respectively. PYY(3-36) (15 pmol x kg(-1) x min(-1)) inhibited food intake by 32%; ghrelin at 15 and 50 pmol x kg(-1) x min(-1) attenuated this effect by 54 and 74%, respectively. A 20-min intravenous infusion of ghrelin (15-150 pmol x kg(-1) x min(-1)) attenuated GLP-1-and PYY(3-36)-induced inhibition of gastric emptying of saline by 6-29%. Thus, intravenous infusion of ghrelin during the early dark period stimulates food intake in freely feeding rats by increasing meal frequency, and similar doses of ghrelin attenuate gastric emptying and feeding responses to GLP-1 and PYY(3-36). These results suggest that ghrelin may stimulate food intake in part by attenuating the inhibitory effects of GLP-1 and PYY(3-36) on gastric emptying and food intake.