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 human s have been shown to inhibit gastrointestinal motility and decrease hunger and energy intake. However, these investigations used supraphysiological do ses. The objective of this study was to investigate the effects of a GLP-1 infusion in a physiological dose on appetite sensations, energy intake, gas tric emptying, energy and substrate metabolism. METHODS: Eighteen obese men participated in the placebo-controlled, randomi zed, single-blinded, cross-over study with infusion of GLP-1 or saline. Res ting metabolic rate (RMR) and substrate oxidations were measured by ventila ted hood before and after an energy-fixed breakfast. Gastric emptying was m easured using paracetamol as a marker. Visual analogue scales were used to assess appetite sensations, thirst and comfort throughout the experiment an d palatability of the test meals. Blood was sampled for analysis of hormone s (GLP-1, GLP-2, glucose-dependent insulinotropic polypeptide (GIP), insuli n, glucagon), and substrates (glucose, lactate, non-esterified fatty acids (NEFA), triacylglycerol (TAG)). Ad libitum energy intake at lunch was regis tered. RESULTS: Following the breakfast, GLP-1 infusion suppressed ratings of hung er and prospective food consumption (P < 0.05), whereas all other subjectiv e ratings and ad libitum energy intake were unaffected. RMR, carbohydrate o xidation and gastric emptying rate were lower during the GLP-1 infusion com pared with the saline infusion (P < 0.001, P < 0.05, P < 0.0001, respective ly). All plasma hormone and substrate profiles, except NEFA, were significa ntly reduced by GLP-1 (P < 0.0001). CONCLUSION: It is concluded that GLP-1 in physiological concentrations powe rfully reduces the rate of entry of nutrients into the circulation by a red uction of gastric emptying rate in obese subjects. The effect of GLP-1 on a ppetite and food intake may be beneficial in weight reduction.