A glucagon-like peptide-1 receptor agonist and an antagonist modify macronutrient selection by rats

The hypothesis that peripheral glucagon-like peptide-1 (GLP-1) is a regulator of both food intake and macronutrient selection in rats was tested by administration of its antagonist, exendin 9-39, and its agonist, exendin 4. The effect of exendin 9-39 given intraperitoneally (i.p.) on food Intake was measured after carbohydrate, protein or fat preloads, and on choice between a protein-free, high carbohydrate (CHO) diet and a high protein, low carbohydrate (PRO) diet. The effect of exendin 4 on selection between the CHO and PRO diets was also investigated. Exendin 9-39 significantly enhanced food intake suppression occurring after glucose, but not after corn oil or albumin preloads. In diet selection studies, exendin 9-39 selectively decreased intake of only the CHO diet. In contrast, exendin 4 decreased intake of only the PRO diet. Thus, we suggest that peripheral GLP-1 plays a role in the regulation of macronutrient selection as well as food intake in rats.