Glucagon-Like Peptide-1 Regulation of Carbohydrate Intake Is Differentially Affected by Obesogenic Diets

The incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in the regulation of appetite by acting as an anorexigenic gut-brain signal. The postprandial release of GLP-1 can be blunted in obese humans and animals. However, it remains unknown whether obesogenic diets with varying fat and carbohydrate content may differentially influence the effectiveness of GLP-1 feedback. To investigate this, male Sprague-Dawley rats were fed a standard (low fat) chow diet, or one of two high-energy diets varying in fat content (45 or 60 kcal%) for 28 weeks. Intake of sucrose and fructose solutions, two commonly added sugars in the Western diet, was then tested in nondeprived rats following administration of the GLP-1 receptor agonist, Exendin-4 (0, 0.5, 1, 2, 3 mu g/kg; s.c.). Exendin-4 dose-dependently reduced short (2h) sucrose and fructose intake. This effect was significantly attenuated in rats fed more dietary fat, despite both diets resulting in obesity. These findings demonstrate that intake of carbohydrates when offered as treats can be regulated by GLP-1 and suggests that dietary fat consumption, rather than extra calories or obesity, may lead to impaired GLP-1 feedback to curb carbohydrate intake. Future studies are warranted to investigate the relevance of these observations to humans and to elucidate the underlying mechanisms.