Regulation of food intake by gastrointestinal peptides

食物摄取是一个关键的生物过程，对哺乳动物的健康有重大影响。了解调节食物摄入的生理机制对于制定治疗人类健康疾病（例如肥胖症）和提高家畜生产力的策略非常重要。食物的消耗刺激胃肠道（肠道）释放大量肽，最终反馈到大脑产生饱腹感。然而，大多数这些信号的作用机制仍有待确定。我的研究计划的总体目标是获得肠脑肽调节食物摄入量和体重的生理机制的基本理解。该提议涉及胰高血糖素样肽-1（7-36）-NH 2 [GLP-1]，一种主要从远端肠分泌的肽，以及生长素释放肽，一种主要从胃分泌的肽。有证据（包括我们自己的一些数据）表明，GLP-1或GLP-1受体类似物可有效减少摄食量和胃排空，而ghrelin可增加许多动物模型和人体的摄食量和胃排空。在本项目中，我们将使用大鼠模型来验证从肠道分泌的GLP-1作为大脑调节食物摄入和胃排空的信号的假设。这一假设为以下具体目标提供了依据：

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: