Interactions between leptin and exendin-4, a glucagon-like peptide-1 agonist, in the regulation of food intake in the rat.
Leptin interplays with other peptides to control feeding behaviour in humans and animals. Using exendin-4, an agonist of glucagon-like peptide-1, we investigated whether leptin modifies its effect on food intake in the rat. In the first series, exendin-4 alone (0.1, 2 or 10 microg per rat), leptin alone (0.1, 2, 10 or 100 microg per rat) or exendin-4 and leptin together (0.1 + 0.1, 2 + 2, 10 + 10, or 2 + 100 microg per rat, respectively) were injected once intraperitoneally. In the second series animals were injected either with exendin-4 (2 microg) alone, leptin (10 microg) alone, or leptin (10 microg) + exendin-4 (2 microg) daily for 5 subsequent days. At the lowest dose used, leptin and exendin-4 injected once together, but not separately, reduced significantly a 24-hour food intake. When used in higher doses, however, leptin did not change the exendin-4-dependent suppressory effect on food consumption. No significant differences in food intake were seen between rats treated repeatedly with exendin-4 only and animals injected with both drugs. Hence, leptin and exendin-4 may act additively to inhibit appetite when present in low concentrations while, at high leptin doses, this effect is abolished. The lack of synergistic effects of exendin-4 and high leptin concentrations on food intake may explain, at least in part, mechanisms responsible for leptin resistance in subjects with hyperleptinaemia.
Bojanowska
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Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Poland. ebojanowska@bg.umed.lodz.pl
Nowak
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A
D000818:Animals; D001066:Appetite / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms / Q000494:pharmacology*
D020738:Leptin; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide