Neural Mechanisms for Control of Food Intake by Circulating and Central GLP-1
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Glucagon-like peptide-1 (GLP-1), an endocrine satiation signal, is secreted by the intestinal `L' cells as well as a small population of neurons in the hindbrain. One of its diverse actions is reduction of food intake. Nevertheless, the sites where circulating and central GLP-1 acts to reduce food intake had not been definitively identified. In chapter one of this dissertation, we tested the hypothesis that vagal afferents are necessary for reduction of food intake by circulating GLP-1 using intact, vagotomized and capsaicin-treated rats. As comparison we also examined reduction of food intake by sulfated CCK-8. We found that intravenous infusion of GLP-1 reduced food intake in control rats and that reduction of intake was not diminished in vagotomized or capsaicin-treated rats. These results indicate that vagal or capsaicin-sensitive non-vagal neurons are not necessary for reduction of food intake by circulating GLP-1 or CCK-8. In chapter two of this dissertation, we tested the hypothesis that the dorsal vagal complex (DVC) is a site that participates in reduction of food intake by peripherally- and centrally-applied GLP-1 receptor agonist, exendin-4, using rats with DVC lesions. We found that DVC lesions attenuated, but did not eliminate reduction of food intake in response to either intraperitoneal or fourth ventricle exendin-4 administration. These results indicate that the DVC participates in reduction of food intake by GLP-1R agonist. Taken together our results indicate that GLP-1 receptors in the brain are responsible for reduction of feeding by circulating GLP-1. Furthermore our results indicate that GLP-1 receptors in the dorsal vagal complex contribute to reduction of food intake by both circulating and centrally administered GLP-1 receptor agonists.