Stress and Body Weight Regulation

压力和体重调节

• 批准号: 7161344
• 负责人: Randall R. Sakai
• 金额: $ 32.02万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7161344
• 关键词: Animal Model; Animals; Body Weight; Body Weight Changes; Body Weight decreased; Body fat; Chronic stress; Complex; Condition; Control Groups; Disease; Down-Regulation; Eating; End Point; Endocrine; Energy Intake; Energy Metabolism; Exposure to; Food Intake Regulation; Health; Home environment; Hormones; Housing; Intervention; Life; Modeling; Morbidity - disease rate; Neurosecretory Systems; Neurotransmitters; Obesity; Physiological; Rattus; Recovery; Regulation; Research; Rodent Model; Secondary to; Social Dominance; Social Hierarchy; Stress; System; Testing; Universities; Weight; energy balance; feeding; insight; neurochemistry; novel; novel strategies; prevent; research study; social; social stress; wasting

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（申请人提供）：食物摄入与体重的调节是一个多因素复杂的相互作用过程。在这些因素中包括动物生活的社会环境，特别是伴随着统治等级制度的社会压力。我们利用一种独特的社会压力动物模型来研究这种社会等级如何影响食物摄入和体重的调节，并揭示社会影响体重的神经内分泌机制。特别是，我们发现，当动物被放置在一个可见的洞穴系统（VBS）中时，我们可以识别从属（SUB）和主导（DOM）动物，并且SUB动物在洞穴中时体重减轻。本提案的重点是测试关于社会压力在下属动物中改变参与食物摄入和体重调节的基本神经内分泌回路的机制的几个假设。拟议的实验对于全面了解食物摄入和体重是如何调节的至关重要。重要的是，该模型为探索应激/HPA系统与体重调节之间复杂而重要的关系提供了一种新的方法。具体目标是：1)确定在SUB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是由负能量平衡改变。通过几个新的对照组进行比较（优势大鼠，自由喂养，配对喂养和体重匹配），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)确定食物摄入的减少和/或能量消耗的增加是否继发于体内脂肪防御量的稳态下调，还是应激激素和神经递质的直接分解代谢作用。3)为了验证在VBS和恢复中的多个慢性应激周期会比暴露于单一事件产生更严重和持久的体重调节系统变化的假设。这项研究对健康的意义是显而易见的。确定参与能量平衡调节的中枢神经系统机制如何被应激改变，对于全面了解应激相关疾病状态和肥胖的合并症至关重要。有趣的是，压力和食物摄入调节都有共同的神经化学系统，本提案试图定义控制每个系统的机制的相互关系和独立性。这一建议的实施将提供对这一调节系统不同层次之间联系的洞察，从而为如何最好地使用多种干预措施来预防或治疗肥胖以及由压力引起的相关疾病提供指导。