Regulation of food intake by gastrointestinal peptides

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Food intake is a key biological process with a major impact on mammalian health. An understanding of the physiological mechanisms regulating food intake is important for developing strategies for treating health disorders of humans (e.g. obesity), and for enhancing the productivity of domestic livestock. The consumption of food stimulates the release of numerous peptides from the gastrointestinal tract (gut) that ultimately feedback to the brain to produce satiety. However, the mechanism(s) of action of a majority of these signals remains to be defined. The overall goal of my research program is to gain a fundamental understanding of the physiological mechanisms by which gut-brain peptides regulate food intake and body weight. This proposal concerns glucagon like peptide-1 (7-36)-NH2 [GLP-1] a peptide secreted primarily from the distal gut, and also ghrelin a peptide secreted mainly from the stomach. There is evidence, including some of our own data, to suggest that GLP-1 or GLP-1 receptor analogues potently reduce food intake and gastric emptying, and that ghrelin increases food intake and gastric emptying in a number of animal models and humans. In this project we will use a rat model for testing the hypothesis that GLP-1 secreted from the gut acts as a signal to the brain to regulate food intake and gastric emptying. This hypothesis provides the basis for the following specific aims: