Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats.
Ghrelin is a new orexigenic and adipogenic peptide primarily produced by the stomach and the hypothalamus. In the present experiment, we determined the circulating ghrelin levels in 60-week old fa/fa Zucker rats with a well-established obesity (n = 12) and in their lean (FA/FA) counterparts (n = 12). We also tested the feeding response of both groups to intra-peritoneal (I.P.) injection of ghrelin agonist and antagonist. Obese rats ate significantly more than the lean rats (21.7 +/- 1.1 vs. 18.3 +/- 0.3 g/day; p < 0.01). Their plasma ghrelin concentration was 35% higher than that in the lean homozygous rats (p < 0.025). GHRP-6 (1 mg/kg I.P, a GHS-R agonist) stimulated food intake in lean but not in obese rats (p < 0.01), whereas [D-Lys)]-GHRP-6 (12 mg/kg I.P., a GHS-R antagonist) decreased food intake in both groups (p < 0.0001). These results indicate that the obese Zucker rat is characterized by an increase in plasma ghrelin concentrations and by an attenuated response to a GHS-R agonist. They support a role for ghrelin in the development of obesity in the absence of leptin signaling.
Beck
Bernard
B
UHP/EA 3453 - IFR 111-Systèmes Neuromodulateurs des Comportements Ingestifs-38, rue Lionnois 54000 Nancy, France.
Richy
Sébastien
S
Stricker-Krongrad
Alain
A
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005508:Food Deprivation; D054439:Ghrelin; D013006:Growth Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D009765:Obesity / Q000097:blood*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D036361:Peptide Hormones / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D051381:Rats; D011924:Rats, Zucker
D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone