Stress and Body Weight Regulation

压力和体重调节

• 批准号: 6838711
• 负责人: Randall R. Sakai
• 金额: $ 33.77万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6838711
• 关键词: animal colony; behavioral /social science research tag; bioenergetics; blood chemistry; body composition; body weight; calorimetry; ethology; homeostasis; in situ hybridization; laboratory rat; neuroendocrine system; neuropeptides; nutrient intake activity; social dominance; stress; weight control; weight loss

DESCRIPTION (provided by applicant): The regulation of food intake and body weight is a complex interaction of multiple factors. Among these factors is the social milieu in which the animal lives and in particular the social stress that accompanies dominance hierarchies. We utilize a unique animal model of social stress to study how such social hierarchies influence the regulation of food intake and body weight and additionally to uncover the neuroendocrine mechanisms that underlie social influences on body weight. In particular, we found that when animals are placed into a visible burrow system (VBS), we can identify the subordinate (SUB) and dominant (DOM) animals and that SUB animals have reduced body weight when they are in the burrow. The focus of this proposal is to test several hypotheses concerning the mechanism by which social stress in subordinate animals alters the fundamental neuroendocrine circuits involved in the regulation of food intake and body weight. The proposed experiments are critical to a complete understanding of how food intake and body weight are regulated. Importantly, the proposed model offers a novel approach for exploring the complicated but vital relationship between the stress/HPA system and body weight regulation. Specific Aims are: 1) To determine whether the weight loss that is observed in SUB is a result of reduced energy intake and/or increased energy expenditure. In addition, we will determine several endocrine and neurochemical endpoints that are altered by negative energy balance. With several novel control groups for comparison (dominant rats, ad lib fed, pair-fed and body weight-matched), we will be able to determine which major systems interact to produce the observed body weight changes. 2) To determine whether the reduced food intake and/or increased energy expenditure of SUB is secondary to a homeostatic down regulation of the defended amount of body fat, or to a direct catabolic action of stress hormones and neurotransmitters. 3) To test the hypothesis that multiple cycles of chronic stress in the VBS and recovery will produce more severe and enduring changes in body weight regulatory systems than exposure to a single episode. The health significance of this research is clear. Determining how CNS mechanisms involved in the regulation of energy balance are altered by stress is critical to a complete understanding of the co-morbidity of stress related disease states and obesity. Interestingly both stress and food intake regulation share common neurochemical systems and this proposal attempts to define both the interrelatedness as well as the independence of the mechanisms that govern each system. The execution of this proposal will provide insight into the connections between different levels of this regulatory system and thereby give direction to how multiple interventions might best be used to prevent or treat obesity and associated conditions resulting from stress.

描述（由申请人提供）：摄食量和体重的调节是多种因素的复杂相互作用。这些因素包括动物生活的社会环境，特别是伴随着统治等级的社会压力。我们利用一个独特的动物模型的社会压力，研究如何这样的社会阶层影响的食物摄入量和体重的调节，此外，揭示神经内分泌机制，社会对体重的影响。特别是，我们发现，当动物被放置到一个可见的洞穴系统（VBS），我们可以识别从属（DOM）和显性（DOM）的动物和动物体重下降，当他们在洞穴中。这项建议的重点是测试几个假设的机制，社会压力在下属动物改变的基本神经内分泌回路参与调节食物摄入量和体重。拟议的实验对于完全理解食物摄入量和体重是如何调节的至关重要。重要的是，该模型为探索压力/HPA系统与体重调节之间复杂但重要的关系提供了一种新方法。具体目标是：1）确定在哺乳动物中观察到的体重减轻是否是能量摄入减少和/或能量消耗增加的结果。此外，我们将确定几个内分泌和神经化学终点，由负能量平衡改变。通过几个新的对照组进行比较（优势大鼠、自由进食、成对进食和体重匹配），我们将能够确定哪些主要系统相互作用产生观察到的体重变化。2)为了确定是否减少食物摄入量和/或增加的能量消耗的肥胖是继发于体内平衡下调的防御量的身体脂肪，或直接分解代谢作用的应激激素和神经递质。3)为了检验以下假设：与暴露于单次事件相比，VBS中的多个周期的慢性应激和恢复将在体重调节系统中产生更严重和持久的变化。这项研究的健康意义是显而易见的。确定参与能量平衡调节的中枢神经系统机制如何被压力改变对于完全理解压力相关疾病状态和肥胖的共病性至关重要。有趣的是，压力和食物摄入调节都有共同的神经化学系统，这个提议试图定义管理每个系统的机制的相互关联性和独立性。该提案的执行将深入了解这一调节系统的不同层面之间的联系，从而指导如何最好地使用多种干预措施来预防或治疗肥胖和压力引起的相关疾病。