GUT-BRAIN MECHANISMS IN DIETARY OBESITY

肥胖是一个主要的健康问题。尽管科学和医疗保健专业人士为了解和成功治疗肥胖做出了相当大的努力，但肥胖的发病率仍在继续上升，与肥胖相关的社会成本令人震惊。这一问题的严重性反映在世界卫生组织和国家卫生研究院最近的调查和目标中。然而，这些努力可能很快就会收到回报，因为近年来发现的两个因素揭示了维持体内特定脂肪量的基本调节系统。这种脂肪量在不同的环境中可能会有所不同，而且在个体之间肯定会有很大的差异。尽管如此，在恒定的环境中，个体严格地维持和保护以脂肪形式储存的总能量的特定数量。关于人类肥胖的第二个主要因素是，当人们经常食用高脂肪含量的饮食时，饮食中储存的脂肪量会随着时间的推移而增加，正如过去三十年来许多国家所发生的那样，肥胖的发病率也会增加。调节身体脂肪的关键负反馈系统失效了。更多的脂肪被储存起来，个体就会朝着肥胖的方向发展。这两个因素的相互作用正是本提案的主题。更具体地说，通过三个相互关联的项目，我们询问高脂肪饮食是如何改变控制体脂的负反馈系统的。驱动假说的这个或任何或所有几个层次的控制。项目1探索肠道对摄入脂肪的处理，并考虑控制膳食大小的膳食相关信号的产生和受体。项目2研究大脑对肥胖指示信号的产生和接收。最后，项目3考虑控制食物摄入和新陈代谢的脑神经递质系统。确定介导高脂肪饮食引起的肥胖的调节过程是这个项目的主要目标。

Obesity is a major health problem. For in spite of considerable effort by the scientific and healthcare professions to understand and successfully treat obesity, its incidence continues to rise and the obesity-related costs to society are staggering. The enormity of the problem is reflected in recent surveys and goals of the World Health Organization and the National Institutes of Health. The effort may soon be paying dividends, however, in that two factors have come to light in recent years that shed light on fundamental regulatory system that works to maintain a particular amount of fat in the body. This amount of fat may vary in different environments, and certainly varies considerably among individuals. Nonetheless, in a constant environment, individuals rigorously maintain and defend a particular amount of total stored energy in the form of fat. The second major factor that has come to light concerning human obesity is that when a diet with a high fat content is consumed on a regular basis, the amount of stored fat in the diet increases over time, as has occurred in many nations over the past thirty years, the incidence of obesity also increases. The key negative feedback system that regulates body fat slips. More fat is stored and the individual moves along the scale toward obesity. It is the interaction of these two factors that is the subject of this proposal. More specifically, over three interrelated projects, we ask how consumption of a high-fat diet modifies the negative feedback system that controls body fat. The driving hypothesis of this or any or all of several levels of control. Project 1 explores the processing of ingested fat by the gut and considers the generation and receptor of meal-related signals that control meal size. Project 2 investigates the generation and reception by the brain of adiposity-indicating signals. Finally, Project 3 considers brain neurotransmitter systems that control food intake and metabolism. Identifying the regulatory processes that mediate high-fat diet-induced obesity is the major goal of this project.