The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans.

Abstract

To investigate the effects of a near-physiological peripheral glucagon-like peptide-1 (GLP-1) infusion, during and after a breakfast of fixed energy content, on resting energy expenditure, substrate oxidation and metabolism and the desire to eat specific types of food in humans. A placebo-controlled, randomized, blinded, cross-over study. Infusion (GLP-1, 50 pmol/kg x h or saline) was started simultaneously with initiation of the test meals. 20 healthy, normal weight (body mass index 20.3-25.7 kg/m2) men of 20-31 y of age. Energy expenditure and substrate oxidations were measured before and for 4 h after standard breakfast (20% of calculated daily energy requirements, 50% of energy from carbohydrates, 37% of energy from fat and 13% of energy from protein) using a ventilated hood system. Visual analogue scales were used throughout the experiment to assess the desire to eat specific types of food and the palatability of the test meals. Blood was sampled throughout the day for analysis of plasma hormone and substrate concentrations. Diet-induced thermogenesis (DIT) was lower (47%) on the GLP-1 infusion than on the saline infusion (P < 0.0001). This was due to a lower carbohydrate oxidation (P < 0.01). No differences in fat oxidation or total 4 h protein oxidation were observed. All hormone and substrate profiles except non-esterified fatty acids (NEFA) and cholecystokinin (CCK) were significantly suppressed (GLP-2 completely suppressed) during the GLP-1 infusion, whereas profiles of NEFA and CCK differed in time course during the two treatments (treatment x time effect), P < 0.0001). GLP-1 infusion also suppressed the desire to eat all food types following the breakfast (treatment effect: P < 0.05). Peripheral GLP-1 decreased DIT and carbohydrate oxidation, probably secondary to a delayed absorption of nutrients, since substrate and hormone concentrations in plasma were suppressed during GLP-1 infusion. Endogenous secretion of GLP-1 and GLP-2 was completely suppressed by GLP-1 infusion. Finally, the desire to eat any type of food was decreased by exogenous administrated GLP-1.