Stress and Body Weight Regulation

压力和体重调节

• 批准号: 7886306
• 负责人: Randall R. Sakai
• 金额: $ 10.09万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7886306
• 关键词: Adipose tissue; Affect; Animals; Behavior; Behavioral; Biological Models; Blood; Body Weight; Characteristics; Chronic; Chronic stress; Collection; Data; Development; Diet; Dietary Fats; Eating; Endocrine; Epidemiology; Excision; Exposure to; Gender; Genetic; Genetic Predisposition to Disease; Glucose; Glucose Transporter; Homeostasis; Housing; Human; Laboratories; Link; Macronutrients Nutrition; Measures; Mediator of activation protein; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Modeling; Neuropeptides; Neurosecretory Systems; Obesity; Obesity associated disease; Overweight; Pattern; Physiology; Rattus; Recovery; Regulation; Rodent; Secondary to; Social Dominance; Societies; Stress; Symptoms; System; Testing; Tissues; Visceral; enhancing factor; glucose tolerance; improved; insight; male; prevent; public health relevance; response; social stress

DESCRIPTION (provided by applicant): Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. We have established the visible burrow system (VBS) model of chronic social stress in our laboratory. In the VBS, mixed gender colonies of rats are housed for 2-week periods during which male rats of the colony quickly develop a dominance hierarchy resulting in subordinate (SUB) and dominant (DOM) animals. We found that SUB animals have reduced body weight during social stress. With repeated, intermittent exposures to social stress in the VBS followed by periods of recovery, SUB rats progressively develop characteristics of obesity that occur, in part, through neuroendocrine alterations and changes in food intake, and predispose the animals to develop other symptoms of the metabolic syndrome. Thus, the VBS model offers a naturalistic paradigm for rigorously examining causal factors that enhance (or diminish) the interaction of social stress with metabolic regulation, while also allowing sophisticated analyses of the control systems involved. We are therefore proposing to continue using the VBS with the following three specific aims. Specific aims are: 1.) To test the hypothesis that SUB have improved glucose tolerance despite having greater adiposity following repeated cycles of chronic social stress and recovery, and that this is due in part to increased glucose removal from the blood; and that this in turn is secondary to altered expression of glucose transporters (GLUT) in key tissues. We further hypothesize that over a long-term recovery period following the final cycle of social stress, SUB will become more obese and revert to worsened glucose tolerance, 2.) To test the hypothesis that diet composition, macronutrient availability, or meal patterns, or a combination of these parameters, alters the metabolic consequences of social stress. Specifically, increased dietary fat is hypothesized to exacerbate the tendency for SUB to regain body weight preferentially as visceral adipose tissue during recovery from the VBS. Endocrine and neuropeptide mediators of stress and energy homeostasis will be determined in response to dietary manipulations prior to, during, and after episodes of social stress, 3) determine whether genetic susceptibility to diet-induced obesity affects the behavioral, neuroendocrine, neuropeptide, and metabolic consequences resulting from social stress. This collection of studies have direct human significance in understanding how chronic stress and recovery from stress affects changes in behavior, physiology, and metabolism associated with obesity and its associated metabolic disorders. PUBLIC HEALTH RELEVANCE Social stress is prevalent in many facets of modern society and a well documented consequence of social stress is the development of obesity. We have developed a laboratory model, the visible burrow system (VBS), to study the effects of social stress in rodents in which we find that during recovery from repeated bouts of social stress, rats develop symptoms of metabolic syndrome similar to those observed in humans such as altered endocrine measures and increased visceral adiposity. Using this naturalistic model allows study of interactions between social stress and metabolism, thereby providing insight toward therapies used to treat and prevent obesity and related diseases in humans.

描述(申请人提供)：社会压力普遍存在于现代社会的许多方面。流行病学数据表明，压力与超重、肥胖和代谢性疾病的发展有关。我们在实验室建立了慢性社会应激的可见洞穴系统(VBS)模型。在VBS中，混合性别的大鼠群体被安置两周，在此期间群体中的雄性大鼠迅速形成优势等级，从而产生从属(亚)和优势(DOM)动物。我们发现，在社会压力下，亚动物的体重有所减轻。随着VBS中反复、间歇性的社会应激暴露，并在恢复期，亚大鼠逐渐发展出肥胖的特征，部分通过神经内分泌改变和食物摄入量的改变发生，并使动物容易发展为代谢综合征的其他症状。因此，VBS模型提供了一个自然主义的范式，用于严格检查增强(或减弱)社会压力与代谢调节相互作用的因果因素，同时也允许对涉及的控制系统进行复杂的分析。因此，我们建议继续使用VBS，有以下三个具体目标。具体目标是：1.)为了验证这样一种假设，即在反复的慢性社会压力和康复周期后，Subs虽然肥胖程度更高，但仍改善了糖耐量，部分原因是血液中葡萄糖的清除增加；这反过来又是关键组织中葡萄糖转运体(GLUT)表达变化的次要原因。我们进一步假设，在社会压力的最后一个周期之后的长期恢复期内，SUB将变得更加肥胖，并恢复到更差的糖耐量。为了检验饮食结构、大量营养素的可获得性或膳食模式，或这些参数的组合会改变社会压力的新陈代谢后果这一假设。具体地说，增加膳食脂肪被假设为加剧了Subs在从VBS恢复期间优先作为内脏脂肪组织恢复体重的趋势。应激和能量平衡的内分泌和神经肽介体将在社会应激之前、期间和之后根据饮食操作的反应来确定，3)确定饮食诱导肥胖的遗传易感性是否影响社会应激导致的行为、神经内分泌、神经肽和代谢后果。这一系列研究对理解慢性压力和压力恢复如何影响与肥胖及其相关代谢紊乱相关的行为、生理和新陈代谢变化具有直接的人类意义。与公共健康相关社会压力在现代社会的许多方面都很普遍，社会压力的一个众所周知的后果是肥胖的发展。我们开发了一个实验室模型，可见洞穴系统(VBS)，用于研究社会应激对啮齿动物的影响。在该模型中，我们发现，在反复的社会应激恢复过程中，大鼠会出现与人类相似的代谢综合征症状，如内分泌指标改变和内脏肥胖症增加。使用这一自然主义模型可以研究社会压力和新陈代谢之间的相互作用，从而为治疗和预防人类肥胖及相关疾病提供洞察力。