TY - JOUR
T1 - The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size
AU - Scott, Karen A.
AU - Moran, Timothy H.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Intestinal peptides
KW - Macaca mulatta
KW - Meal patterns
KW - Satiety
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U2 - 10.1152/ajpregu.00323.2007
DO - 10.1152/ajpregu.00323.2007
M3 - Article
C2 - 17581835
AN - SCOPUS:34548390977
SN - 0363-6119
VL - 293
SP - R983-R987
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 3
ER -