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（由申请人提供）：社会压力在现代社会的许多方面都很普遍。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，将大鼠的混合性别群体圈养2周，在此期间，殖民地的雄性大鼠迅速形成优势等级，导致从属（subordinate）动物和优势（dominant）动物。我们发现，在社会压力下，哺乳动物的体重会减轻。在VBS中反复、间歇性地暴露于社会压力，随后是恢复期，大白鼠逐渐发展出肥胖的特征，这种特征部分是通过神经内分泌改变和食物摄入的变化发生的，并使动物容易发展出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，严格检查因果因素，增强（或减少）的相互作用，社会压力与代谢调节，同时也允许复杂的分析所涉及的控制系统。因此，我们建议继续采用自愿离职计划，以达致以下三个具体目的。具体目标是：（1）检验以下假设：尽管在慢性社会压力和恢复的重复循环后肥胖程度更高，但糖尿病患者的葡萄糖耐量得到改善，这部分是由于血液中葡萄糖清除增加;而这反过来又继发于关键组织中葡萄糖转运蛋白（GLUT）表达的改变。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，肥胖症患者将变得更加肥胖，并恢复到葡萄糖耐量恶化的状态。为了验证这一假设，饮食组成，宏量营养素的可用性，或膳食模式，或这些参数的组合，改变社会压力的代谢后果。具体而言，膳食脂肪增加被假设为加剧了VBS恢复期间，肥胖者优先以内脏脂肪组织的形式恢复体重的趋势。在社会压力发作之前、期间和之后，将响应于饮食操纵来确定压力和能量稳态的内分泌和神经肽介质，3）确定对饮食诱导的肥胖的遗传易感性是否影响由社会压力引起的行为、神经内分泌、神经肽和代谢后果。这些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、生理和代谢变化具有直接的人类意义。社会压力普遍存在于现代社会的许多方面，社会压力的一个有据可查的后果是肥胖的发展。我们已经开发了一个实验室模型，可见洞穴系统（VBS），研究社会压力对啮齿动物的影响，我们发现，在从反复发作的社会压力中恢复的过程中，大鼠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脂肪增多。使用这种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和相关疾病的疗法提供见解。