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

OBJECTIVE: To investigate the effects of a near-physiological peripheral gl ucagon-like peptide-1 (GLP-1) infusion, during and after a breakfast of fix ed energy content, on resting energy expenditure, substrate oxidation and m etabolism and the desire to eat specific types of food in humans. DESIGN: A placebo-controlled, randomized, blinded, cross-over study. Infusi on (GLP-1, 50 pmol/kg x h or saline) was started simultaneously with initia tion of the test meals. SUBJECTS: 20 healthy, normal weight (body mass index 20.3-25.7 kg/m(2)) men of 20-31 y of age. MEASUREMENTS: Energy expenditure and substrate oxidations were measured bef ore and for 4h after standard breakfast (20% of calculated daily energy req uirements, 50% of energy from carbohydrates, 37% of energy from fat and 13% of energy from protein) using a ventilated hood system. Visual analogue sc ales were used throughout the experiment to assess the desire to eat specif ic types of food and the palatability of the test meals. Blood was sampled throughout the day for analysis of plasma hormone and substrate concentrati ons. RESULTS: Diet-induced thermogenesis (DIT) was lower (47%) on the GLP-1 infu sion than on the saline infusion (P < 0.0001). This was due to a lower carb ohydrate oxidation (P < 0.01). No differences in fat oxidation or total 4h protein oxidation were observed. All hormone and substrate profiles except non-esterified fatty acids (NEFA) and cholecystokinin (CCK) were significan tly suppressed (GLP-2 completely suppressed) during the GLP-1 infusion, whe reas profiles of NEFA and CCK differed in time course during the two treatm ents (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). CONCLUSION: peripheral GLP-1 decreased DIT and carbohydrate oxidation, prob ably secondary to a delayed absorption of nutrients, since substrate and ho rmone concentrations in plasma were suppressed during GLP-1 infusion. Endog enous secretion of GLP-1 and GLP-2 was completely suppressed by GLP-9 infus ion. Finally, the desire to eat any type of food was decreased by exogenous administrated GLP-1.