Pathways Linking Reduced Sleep Duration and Quality to Obesity Risk

睡眠时间和质量减少与肥胖风险之间的联系途径

• 批准号: 7173940
• 负责人: Esra Tasali
• 金额: $ 53.46万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173940
• 关键词: appetite; appetite regulatory center; behavior test; bioenergetics; blood glucose; body composition; body weight; brain imaging /visualization /scanning; central nervous system; clinical research; disease /disorder etiology; disease /disorder proneness /risk; functional magnetic resonance imaging; glucose metabolism; hormone regulation /control mechanism; human subject; hunger; insulin; neuroregulation; nutrient intake activity; nutrition related tag; obesity; pathologic process; peripheral nervous system; positron emission tomography; sleep; sleep deprivation

DESCRIPTION (provided by applicant): Epidemiologic data have shown associations between short sleep duration and elevated body mass index (BMI). So far, the major evidence in support of a causal mechanism comes from our laboratory studies of healthy young adults submitted to sleep restriction, showing that short sleep results in altered glucose regulation, decreased leptin levels, increased ghrelin levels, and increased hunger and appetite, suggesting an increased risk of weight gain. The majority of the epidemiologic studies did not control for sleep quality. Yet, many adults who regularly curtail their sleep do not enjoy the sleep quality of healthy young subjects. In particular, reduced sleep quality is typical of normal aging and is highly prevalent in overweight and obese individuals. We have recently obtained important new data demonstrating that experimental reductions of sleep quality without change in sleep duration results in alterations of glucose and appetite regulation that could also lead to an increased risk of obesity. Furthermore, our previous work has shown that decreased sleep quality is an intrinsic consequence of recurrent sleep restriction. These findings indicate that reduced sleep quality may be part of the mechanisms linking short sleep and obesity risk. We therefore propose to obtain causative evidence linking short sleep, either of normal or of impaired quality, to alterations in specific central nervous system and peripheral pathways regulating energy intake. Normal young adults will be studied under 3 controlled laboratory conditions: 5 days (i.e. mimicking one work week) with undisturbed sleep (8.5hrs in bed; "baseline"), 5days with short undisturbed sleep (4.5 hrs in bed; "short sleep") and 5 days of short sleep with experimental fragmentation of NREM sleep (4.5 hrs in bed; "fragmented short sleep"). Both the "short sleep" and "fragmented short sleep" conditions will be followed by 2 nights of undisturbed recovery sleep with 9 hours in bed. The studies will combine brain imaging by PET and fMRI, estimations of sympatho-vagal balance, measurements of orexigenic and anorexigenic factors, cytokines and adipokines, continuous assessment of glucose levels via subcutaneous sensors, in vitro studies of insulin signaling in adipocytes from fat biopsies, and behavioral expression of hunger and food intake. A multi-disciplinary group of expert investigators will collaborate to test the role of specific pathways in the link between short/poor sleep and the increased risk of obesity.

描述（由申请人提供）： 流行病学数据表明，短睡眠持续时间与升高体重指数（BMI）之间的关联。到目前为止，支持因果机制的主要证据来自我们对健康的年轻人进行睡眠限制的实验室研究，这表明短睡眠会导致葡萄糖调节的改变，瘦素水平降低，植物素水平升高，饥饿和食欲增加，表明体重增加的风险增加。大多数流行病学研究无法控制睡眠质量。然而，许多定期减少睡眠的成年人并不享受健康的年轻受试者的睡眠质量。特别是，睡眠质量降低是正常衰老的典型特征，并且在超重和肥胖的个体中非常普遍。我们最近获得了重要的新数据，表明睡眠质量的实验降低而不会改变睡眠持续时间会导致葡萄糖和食欲调节的改变，这也可能导致肥胖风险增加。此外，我们以前的工作表明，睡眠质量降低是复发性睡眠限制的内在结果。这些发现表明，睡眠质量降低可能是连接短睡眠和肥胖风险的机制的一部分。因此，我们建议获得与特定的中枢神经系统和调节能量摄入的特定中枢神经系统和周围途径的改变，以将短睡眠（正常或受损质量的短睡眠）联系起来。将在3个受控的实验室条件下对正常的年轻人进行研究：5天（即模仿一个工作一周）与不受干扰的睡眠（床上8.5小时；“基线”），短暂不受干扰的睡眠（4.5 hr床；床上4.5小时；“短睡眠”）和短睡眠的睡眠时间短5天，睡眠不足（4.5 hrem speart in Speart in 4.5 hr in; 4.5 hr in; 4.5 hr in;; “短睡眠”和“零散的短睡眠”条件都将在床上9个小时内进行2晚不受干扰的恢复睡眠。这些研究将结合通过PET和FMRI的大脑成像，交感神经平衡的估计，对甲状腺素和厌食性因素的测量，细胞因子和脂肪因子，通过皮下传感器对葡萄糖水平的连续评估，在脂肪细胞中的胰岛素信号在脂肪中的胰岛素研究中的胰岛素研究和行为表达效果和食物效果和食物效果和食物效果和食物效果和食物效果和食物的效果和食物效果。一个多学科的专家研究人员将合作测试特定途径在短/不良睡眠与肥胖风险增加之间的联系中的作用。