An Interaction between Hypothalamic Glucagon-Like Peptide-1 and Macronutrient Composition Determines Food Intake in Rats

Glucagon-like peptide-1 (GLP-1) release in response to food ingestion has been associated with decreased food intake. In the present study, we tested the hypothesis that the feeding response to GLP-1 injection into the hypothalamic paraventricular nucleus (PVN) is influenced by the macronutrient composition of the food consumed. In the first experiment, rats were injected with GLP-1 (0.2 microg) or saline (0.5 microL) in the PVN at dark onset (1800 h), and food intake from a maintenance diet (18% protein) was measured at 1, 2 and 14 h. In Experiment 2, after GLP-1 injection, rats were fed a carbohydrate (protein-free) diet for the first 2 h or gavaged with glucose (1.4 g/5 mL). In Experiment 3, after GLP-1 injection, rats were fed a protein (50%) diet for the first 2 h, or were preloaded with egg albumin (1.0 g). In the last experiment, GLP-1 was given after corn oil gavage (2.4 g). GLP-1 injection resulted in a reduced consumption of the maintenance diet from 2 to 14 h. The decreased food intake from 2 to 14 h after GLP-1 administration occurred after carbohydrate intake, either by meal or preloads, but not after protein intake, either as a meal or preload. A transient interaction of GLP-1 with a corn oil gavage was detected but only in early feeding (0-2 h). We conclude that the effect of GLP-1 injected in the PVN on food intake is influenced by the macronutrient composition of the food consumed. Carbohydrate enhances, protein blocks and corn oil has a transient effect on the suppression of food intake caused by GLP-1 in the PVN.