Stress and Body Weight Regulation

压力和体重调节

• 批准号: 7643335
• 负责人: Randall R. Sakai
• 金额: $ 32.81万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643335
• 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普遍存在。流行病学数据表明，压力与超重，肥胖和代谢疾病的发展有关。我们已经在实验室中建立了慢性社会压力的可见洞穴系统（VBS）模型。在VBS中，将大鼠的混合性别菌落饲养为2周，在此期间，菌落的雄性大鼠迅速发展出占优势层次结构，从而导致下属（sub）和占主导地位（DOM）动物。我们发现，在社会压力期间，亚动物减轻了体重。随着在VBS中反复，间歇性暴露于社会压力，随后是恢复时期，子大鼠逐渐发展出肥胖的特征，这些特征部分通过神经内分泌的改变和食物摄入的变化而发生，并使动物倾向于发展代谢综合征的其他症状。因此，VBS模型提供了一种自然主义的范式，用于严格检查因果因素，从而增强（或减少）社会压力与代谢调节的相互作用，同时还允许对所涉及的控制系统进行复杂的分析。因此，我们建议继续使用以下三个特定目的使用VBS。具体目的是：1。）检验以下假设：尽管在慢性社会压力和恢复的反复循环中反复进行肥胖，但葡萄糖的耐受性提高了，这部分是由于从血液中清除了葡萄糖。而这反过来是关键组织中葡萄糖转运蛋白（GLUT）的表达改变的继发。我们进一步假设，在社会压力的最终周期之后的长期恢复期内，Sub将变得更加肥胖，并恢复到恶化的葡萄糖耐量，2。）测试以下假说：饮食组成，大量营养素的可用性或餐食或餐食模式，或者是这些参数的组合，改变了社会压力的代谢后果。具体而言，假设增加的饮食脂肪会加剧Sub在从VBS恢复过程中优先恢复体重为内脏脂肪组织的趋势。在社会压力发作之前，之中和之后，将确定压力和能量稳态的内分泌和神经肽介质，以响应饮食中的操作来确定，3）确定遗传易感性是否会影响行为，神经内分泌，神经肽，神经肽和代谢后果会导致社会压力。这项研究的收集在理解慢性压力和压力中的恢复如何影响行为，生理和代谢与肥胖及其相关的代谢性疾病有关的变化方面具有直接的人类意义。公共卫生相关性社会压力在现代社会的许多方面都普遍存在，社会压力的有充分的后果是肥胖的发展。我们已经开发了一个实验室模型，即可见的洞穴系统（VBS），以研究啮齿动物中社会压力的影响，在这种情况下，我们发现在反复的社会压力中恢复过程中，大鼠出现了代谢综合征的症状，类似于在人类中观察到的诸如内分泌措施改变的人，并增加了内部分泌措施和增加的肥胖。使用这种自然主义模型可以研究社会压力与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。