Stress and Body Weight Regulation

压力和体重调节

• 批准号: 7532075
• 负责人: Randall R. Sakai
• 金额: $ 32.84万
• 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/7532075
• 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; 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; Public Health; Rattus; Recovery; Regulation; Rodent; Secondary to; Social Dominance; Societies; Stress; Symptoms; System; Testing; Tissues; Visceral; Week; enhancing factor; glucose tolerance; improved; insight; male; prevent; 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、肥胖和代谢疾病的发生有关。我们实验室建立了慢性社会压力的可见洞穴系统（VBS）模型。在 VBS 中，混合性别的老鼠群体被圈养两周，在此期间，群体中的雄性老鼠迅速形成统治等级，从而产生从属 (SUB) 和统治 (DOM) 动物。我们发现 SUB 动物在社会压力下体重减轻。在 VBS 中反复、间歇性地暴露于社会压力，然后恢复一段时间后，SUB 大鼠逐渐出现肥胖特征，部分原因是神经内分泌改变和食物摄入量变化，并使动物容易出现代谢综合征的其他症状。因此，VBS 模型提供了一种自然主义范式，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 VBS，以实现以下三个具体目标。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增加，但 SUB 仍改善了葡萄糖耐量，这部分是由于血液中葡萄糖去除量增加；这反过来又是关键组织中葡萄糖转运蛋白（GLUT）表达改变的继发因素。我们进一步假设，在社会压力最后一个周期之后的长期恢复期内，SUB 将变得更加肥胖，并恢复到恶化的葡萄糖耐量，2.) 检验饮食结构、常量营养素可用性或膳食模式或这些参数的组合会改变社会压力的代谢后果的假设。具体来说，假设膳食脂肪的增加会加剧 SUB 在从 VBS 恢复期间优先恢复体重作为内脏脂肪组织的趋势。压力和能量稳态的内分泌和神经肽介质将根据社会压力发作之前、期间和之后的饮食控制来确定，3）确定对饮食引起的肥胖的遗传易感性是否影响社会压力引起的行为、神经内分泌、神经肽和代谢后果。这一系列研究对于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。公共卫生相关性 社会压力在现代社会的许多方面普遍存在，有据可查的社会压力后果是肥胖的发生。我们开发了一种实验室模型，即可见洞穴系统（VBS），来研究啮齿类动物的社会压力的影响，我们发现，在从反复的社会压力中恢复的过程中，老鼠会出现与人类相似的代谢综合征症状，例如内分泌指标改变和内脏肥胖增加。使用这种自然模型可以研究社会压力和新陈代谢之间的相互作用，从而为用于治疗和预防人类肥胖及相关疾病的疗法提供见解。