PATHWAYS LINKING REDUCED SLEEP DURATION AND QUALITY TO OBESITY RISK

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 流行病学数据表明，睡眠时间短与体重指数(BMI)升高有关。到目前为止，支持因果机制的主要证据来自我们对接受睡眠限制的健康年轻人的实验室研究，表明睡眠时间短会导致血糖调节改变，瘦素水平降低，胃促生长素水平增加，饥饿和食欲增加，这表明体重增加的风险增加。大多数流行病学研究没有对睡眠质量进行控制。然而，许多经常减少睡眠的成年人并不享受健康年轻受试者的睡眠质量。特别是，睡眠质量下降是正常衰老的典型现象，在超重和肥胖人群中非常普遍。我们最近获得了重要的新数据，证明在没有改变睡眠时间的情况下，睡眠质量的实验降低会导致血糖和食欲调节的改变，这也可能导致肥胖风险的增加。此外，我们之前的工作表明，睡眠质量下降是反复睡眠限制的内在后果。这些发现表明，睡眠质量下降可能是睡眠不足和肥胖风险之间联系的一部分机制。因此，我们建议获得相关证据，将睡眠质量正常或受损的短睡眠与调节能量摄入的特定中枢神经系统和外周通路的变化联系起来。正常年轻人将在3种受控实验室条件下进行研究：5天(即模拟一周工作)，无干扰睡眠(在床上8.5小时；“基线”)，5天短无干扰睡眠(在床上4.5小时；“短睡眠”)，以及5天短睡眠和实验性的NREM睡眠碎片(在床上4.5小时；“零碎短睡眠”)。在“短睡眠”和“零碎的短睡眠”状态之后，将有两个晚上的无干扰恢复睡眠，在床上休息9个小时。这些研究将结合PET和fMRI的大脑成像、交感迷走神经平衡的估计、食欲和厌食因子、细胞因子和脂肪因子的测量、通过皮下传感器持续评估血糖水平、脂肪活检脂肪细胞中胰岛素信号的体外研究，以及饥饿和食物摄入的行为表达。一个由多学科专家组成的研究小组将合作测试特定途径在睡眠不足和肥胖风险增加之间的联系中所起的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.