Ghrelin Attenuates the Inhibitory Effects of Glucagon-like Peptide-1 and Pe
Ghrelin Attenuates the Inhibitory Effects of Glucagon-like Peptide-1 and Pe
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 · kg · min) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol · kg · min had no effect. GLP-1 (15 pmol · kg · min) inhibited food intake by 35-54%; coinfusion of ghrelin at 50 and 150 pmol · kg · min attenuated this effect by 60 and 64%, respectively. PYY(3-36) (15 pmol · kg · min) inhibited food intake by 32%; ghrelin at 15 and 50 pmol · kg · min attenuated this effect by 54 and 74%, respectively. A 20-min intravenous infusion of ghrelin (15-150 pmol · kg · min) 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.
A growing number of gut-brain peptides have been shown to affect short-term food intake when administered acutely to experimental animals and humans. The 28—amino acid peptide ghrelin stimulates food intake, whereas many other peptides, including cholecystokinin (CCK), glucagon-like peptide-1(7-36) (GLP-1), peptide YY(3-36) [PYY(3-36)], and amylin inhibit food intake. The extent to which ghrelin interacts physiologically or pharmacologically with the other anorexigenic peptides to affect food intake and energy reserves remains to be determined.
Factors that promote gastric distention by inhibiting gastric emptying can reduce food intake. We have provided evidence that CCK, GLP-1, PYY(3-36), and amylin may inhibit food intake in part by inhibiting gastric emptying because each peptide dose-dependently reduces food intake and gastric emptying with similar potency and efficacy in rats. Ghrelin has been reported to stimulate both gastric emptying and food intake. If ghrelin increases food intake in part by accelerating gastric emptying, then it would be important to determine whether similar doses of ghrelin stimulate food intake and gastric emptying.
Bolus administration of ghrelin to rodents during the dark period, their active feeding period, has been reported to produce little if any effect on food intake. Our previous work with anorexigenic peptides suggests that intravenous infusion of these peptides in rats during the early dark period produces a more potent and reliable suppression of feeding than bolus administration. The effects of intravenous infusion of ghrelin under these conditions remain to be determined.
In the current study, we determined 1) the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake and meal patterns in nondeprived rats, 2) the effects of intravenous infusion of ghrelin under the same conditions on anorexigenic responses to intravenous infusions of GLP-1 and PYY(3-36), and 3) the effects of a 20-min intravenous infusion of ghrelin on the inhibitory effects of intravenous infusions of GLP-1 and PYY(3-36) on gastric emptying of saline in food-deprived rats.
Abstract and Introduction
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 · kg · min) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol · kg · min had no effect. GLP-1 (15 pmol · kg · min) inhibited food intake by 35-54%; coinfusion of ghrelin at 50 and 150 pmol · kg · min attenuated this effect by 60 and 64%, respectively. PYY(3-36) (15 pmol · kg · min) inhibited food intake by 32%; ghrelin at 15 and 50 pmol · kg · min attenuated this effect by 54 and 74%, respectively. A 20-min intravenous infusion of ghrelin (15-150 pmol · kg · min) 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.
Inttroduction
A growing number of gut-brain peptides have been shown to affect short-term food intake when administered acutely to experimental animals and humans. The 28—amino acid peptide ghrelin stimulates food intake, whereas many other peptides, including cholecystokinin (CCK), glucagon-like peptide-1(7-36) (GLP-1), peptide YY(3-36) [PYY(3-36)], and amylin inhibit food intake. The extent to which ghrelin interacts physiologically or pharmacologically with the other anorexigenic peptides to affect food intake and energy reserves remains to be determined.
Factors that promote gastric distention by inhibiting gastric emptying can reduce food intake. We have provided evidence that CCK, GLP-1, PYY(3-36), and amylin may inhibit food intake in part by inhibiting gastric emptying because each peptide dose-dependently reduces food intake and gastric emptying with similar potency and efficacy in rats. Ghrelin has been reported to stimulate both gastric emptying and food intake. If ghrelin increases food intake in part by accelerating gastric emptying, then it would be important to determine whether similar doses of ghrelin stimulate food intake and gastric emptying.
Bolus administration of ghrelin to rodents during the dark period, their active feeding period, has been reported to produce little if any effect on food intake. Our previous work with anorexigenic peptides suggests that intravenous infusion of these peptides in rats during the early dark period produces a more potent and reliable suppression of feeding than bolus administration. The effects of intravenous infusion of ghrelin under these conditions remain to be determined.
In the current study, we determined 1) the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake and meal patterns in nondeprived rats, 2) the effects of intravenous infusion of ghrelin under the same conditions on anorexigenic responses to intravenous infusions of GLP-1 and PYY(3-36), and 3) the effects of a 20-min intravenous infusion of ghrelin on the inhibitory effects of intravenous infusions of GLP-1 and PYY(3-36) on gastric emptying of saline in food-deprived rats.
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