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APPETITE, OBESITY, DIGESTION, AND METABOLISM

The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland

Submitted 8 May 2007 ; accepted in final form 15 June 2007

ABSTRACT

Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques (n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 µg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 µg/kg dose completely preventing feeding during the 6-h period and the 0.10 µg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 µg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 µg/kg doses (P < 0.05). Day 2 and 3intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 µg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.

intestinal peptides; satiety; meal patterns; Macaca mulatta