The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

OBJECTIVE: Peripheral infusions of glucagon-like peptide-1 (GLP-1) in humans have been shown to inhibit gastrointestinal motility and decrease hunger and energy intake. However, these investigations used supraphysiological doses. The objective of this study was to investigate the effects of a GLP-1 infusion in a physiological dose on appetite sensations, energy intake, gastric emptying, energy and substrate metabolism. METHODS: Eighteen obese men participated in the placebo-controlled, randomized, single-blinded, cross-over study with infusion of GLP-1 or saline. Resting metabolic rate (RMR) and substrate oxidations were measured by ventilated hood before and after an energy-fixed breakfast. Gastric emptying was measured using paracetamol as a marker. Visual analogue scales were used to assess appetite sensations, thirst and comfort throughout the experiment and palatability of the test meals. Blood was sampled for analysis of hormones (GLP-1, GLP-2, glucose-dependent insulinotropic polypeptide (GIP), insulin, glucagon), and substrates (glucose, lactate, non-esterified fatty acids (NEFA), triacylglycerol (TAG)). Ad libitum energy intake at lunch was registered. RESULTS: Following the breakfast, GLP-1 infusion suppressed ratings of hunger and prospective food consumption (P < 0.05), whereas all other subjective ratings and ad libitum energy intake were unaffected. RMR, carbohydrate oxidation and gastric emptying rate were lower during the GLP-1 infusion compared with the saline infusion (P < 0.001, P < 0.05, P < 0.0001, respectively). All plasma hormone and substrate profiles, except NEFA, were significantly reduced by GLP-1 (P < 0.0001). CONCLUSION: It is concluded that GLP-1 in physiological concentrations powerfully reduces the rate of entry of nutrients into the circulation by a reduction of gastric emptying rate in obese subjects. The effect of GLP-1 on appetite and food intake may be beneficial in weight reduction.