Administrative Core

行政核心

• 批准号: 7089243
• 负责人: STEPHEN C WOODS
• 金额: $ 4.61万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089243
• 关键词: Administrative; Core

DESCRIPTION (provided by applicant): 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. Two factors have come to light in recent years that shed light on fundamental aspects of the problem and may hold a key for future therapies. The first factor is that the body possesses a remarkably efficient regulatory system that works to maintain a particular amount of fat in the body. This amount of fat may vary in different environments, and it certainly varies considerably among individuals. Nonetheless, in a constant environment, individuals rigorously defend a particular amount of total stored energy in the form of fat. The second major factor concerning human obesity is that when a diet with a high saturated fat content is consumed on a regular basis, the amount of stored fat that the body defends increases. Hence, epidemiological studies have identified a significant correlation between average dietary fat intake and the incidence of obesity and its related complications mad risk factors among nations. And when the average amount of 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 point is that when individuals are exposed, on a chronic basis, to a higher average level of dietary saturated fat, the otherwise incredibly robust negative feedback system that regulates body fat slips. More fat is stored and the individual moves 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 saturated fat diet modifies a number of critical factors that determine body fat and the predisposition to become diabetic. Project 1 focuses on how the gut and CNS protein Apo A-IV regulate food intake and can be altered by diets with different amounts and types of fat. Project 2 tests several hypotheses about how saturated versus monounsaturated fats influence the adaptation of the pancreatic beta-cell to increasing insulin resistance. Project 3 seeks to elucidate the mechanisms in the CNS that contribute to the defense of increased body fat that occurs on high saturated fat diet.

描述（由申请人提供）： 尽管科学和医疗保健行业付出了巨大的努力，以理解和成功治疗肥胖症，但其发病率仍在上升，与肥胖相关的社会成本令人震惊。该问题的巨大性反映在世界卫生组织和美国国立卫生研究院的最近调查和目标中。近年来，已经揭示了两个因素，揭示了问题的基本方面，并可能是未来疗法的关键。第一个因素是人体具有非常有效的调节系统，该系统可维持体内特定脂肪。这种脂肪在不同的环境中可能有所不同，并且在个体之间肯定会有很大的不同。尽管如此，在恒定的环境中，个人以脂肪的形式严格捍卫特定数量的总存储能量。关于人肥胖的第二个主要因素是，当定期食用饱和脂肪含量高的饮食时，人体防御的储存脂肪量会增加。因此，流行病学研究已经确定了平均饮食脂肪摄入量与肥胖症的发生率及其相关并发症的发生率之间存在显着相关性。而且，当饮食中的平均脂肪随着时间的流逝而增加，就像过去三十年来许多国家一样，肥胖的发生率也会增加。关键点是，当个人长期暴露于饮食饱和脂肪的平均水平较高时，可以调节体内脂肪滑移的原本令人难以置信的负面反馈系统。储存更多的脂肪，并且个人向肥胖转向。这两个因素的相互作用是该提案的主题。更具体地说，在三个相互关联的项目中，我们询问高饱和脂肪饮食的消费如何改变许多关键因素，这些因素决定了体内脂肪，并倾向于成为糖尿病。项目1的重点是肠道和中枢神经系统蛋白Apo A-IV如何调节食物摄入量，并且可以通过不同量和类型脂肪的饮食来改变。项目2检验了几种假设，即饱和脂肪与单不饱和脂肪如何影响胰腺β细胞对增加胰岛素耐药性的适应。项目3旨在阐明中枢神经系统中的机制，这些机制有助于捍卫高饱和脂肪饮食上增加体内脂肪的增加。