Impact of Sleep on Feeding and the Metabolic Syndrome

睡眠对进食和代谢综合症的影响

• 批准号: 6707038
• 负责人: Joseph Bass
• 金额: $ 36.63万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6707038
• 关键词: appetite; bioenergetics; biological clocks; circadian rhythms; gene environment interaction; gene expression; genetic strain; hormone regulation /control mechanism; hormone sensitivity /resistance; hypothalamic pituitary adrenal axis; insulin; laboratory mouse; leptin; metabolic syndrome; neuropeptides; nutrient intake activity; nutrition related tag; sleep deprivation; weight gain

DESCRIPTION (provided by applicant): Over the past two decades, an increased prevalence of sleep deprivation in the US has become a major public health challenge. Sleep deprivation been implicated in the epidemic of the metabolic syndrome, a condition characterized by insulin resistance, hyperlipidemia, cardiovascular disease and hypertension. Presently, 30% of the US population is overweight or obese and diabetes affects nearly 17% of persons over the age of 65. Recent clinical research indicates that sleep deprivation may pose a risk for the development of diabetes and the metabolic syndrome, however the underlying physiological and pathophysiological basis for the connection between sleep and metabolic homeostasis remains incompletely understood. This application proposes to exploit a novel experimental model of acute and chronic partial sleep deprivation in order to dissect the link between sleep loss and the metabolic syndrome. Already, we have found that chronic partial sleep loss in our animal model reproduces features of the metabolic syndrome including changes in hypothalamo-adrenal axis, decreased leptin and increased fatty acids. We have also made exciting discovery that suggest a role for alterations in the biological clock and clock regulated metabolic pathways that may lead to the metabolic syndrome. We now propose to apply the model we have developed together with molecular genetic tools to investigate the basic mechanisms that link sleep, circadian rhythms, food intake and energy homeostasis. Insight gained from these studies will provide new strategies to prevent metabolic complications associated with sleep deprivation and uncover novel metabolic targets for treatment of obesity and its co-morbidities.

描述（由申请人提供）： 在过去的二十年里，美国睡眠不足现象日益普遍，已成为一项重大的公共卫生挑战。睡眠不足与代谢综合征的流行有关，代谢综合征是一种以胰岛素抵抗、高脂血症、心血管疾病和高血压为特征的疾病。目前，30% 的美国人口超重或肥胖，近 17% 的 65 岁以上人口受到糖尿病的影响。最近的临床研究表明，睡眠不足可能会带来患糖尿病和代谢综合征的风险，但其根本原因是：睡眠与代谢稳态之间联系的生理和病理生理学基础仍不完全清楚。该申请提出开发一种急性和慢性部分睡眠剥夺的新实验模型，以剖析睡眠不足与代谢综合征之间的联系。我们已经发现，在我们的动物模型中，慢性部分睡眠缺失会重现代谢综合征的特征，包括下丘脑-肾上腺轴的变化、瘦素减少和脂肪酸增加。我们还取得了令人兴奋的发现，表明生物钟和生物钟调节代谢途径的改变可能导致代谢综合征。我们现在建议应用我们与分子遗传学工具一起开发的模型来研究连接睡眠、昼夜节律、食物摄入和能量稳态的基本机制。从这些研究中获得的见解将为预防与睡眠剥夺相关的代谢并发症提供新策略，并发现治疗肥胖及其并发症的新代谢目标。