Mechanisms of Insufficient Sleep Contributing to Metabolic Disease Risk and Impact from Weekend Recovery Sleep

项目摘要/ABSRACT 肥胖是一种流行病，大约50%的美国人口患有糖尿病或糖尿病前期。此外，死亡 患有各种原因的糖尿病患者的发病率是未确诊糖尿病患者的1.5倍。 2012年，美国糖尿病造成的经济损失为2450亿美元。因此，糖尿病和相关的代谢性疾病 代表着重大的公共卫生和经济负担。夜间睡眠时间短和未经治疗的睡眠障碍 现在被认为是代谢性疾病的危险因素，超过50%的美国人睡眠时间少于 建议的7小时/晚，以及影响5000万至7000万美国人的睡眠和觉醒障碍。 然而，睡眠不足导致代谢性疾病的生化机制在很大程度上是未知的， 阻碍针对负代谢的新的有效对策的发展 失眠的后果。此外，尚不清楚共同的和自我选择的对策是否 周末恢复睡眠可以减轻睡眠不足对新陈代谢的负面影响。因此，我建议 确定睡眠不足对潜在代谢失调机制的影响，并确定 “周末恢复”睡眠对这些机制的影响。拟议的项目将利用代谢组学来 分析正在进行的实验室研究中的血浆样本，调查胰岛素敏感性和能量平衡 在睡眠不足期间，然后是周末恢复睡眠。在我的初步研究工作指导下，我将 使用靶向和非靶向代谢组学方法来确定受影响的代谢物和代谢途径 睡眠不足和周末恢复睡眠。此外，非定向发现方法可以识别 潜在的“生物标记物”会随着睡眠不足和“周末恢复”睡眠而改变。我提出的研究结果将会有所帮助 通知未来的验证和睡眠对策调查，包括测试高危人群(即 肥胖、糖尿病前期、倒班工人)。这项拟议的F32奖是对2011年NIH睡眠计划的一个关键目标的回应 障碍研究计划“使睡眠和昼夜节律研究培训在交叉领域为科学提供信息 领域，加快发现的步伐，并将增强疗法从工作台转移到床边 社区“，旨在推进我在睡眠、昼夜生理学和代谢组学方面的培训，以 增强我成功获得NIH职业发展K奖的潜力。

PROJECT SUMMARY/ABSRACT Obesity is epidemic and ~50% of the United States population has diabetes or prediabetes. Furthermore, death rates from all causes are ~1.5 times greater for individuals with versus without diagnosed diabetes and the economic cost of diabetes in the US was $245 billion in 2012. Thus, diabetes and associated metabolic diseases represent major public health and economic burdens. Short nightly sleep duration and untreated sleep disorders are now recognized as risk factors for metabolic diseases with more than 50% of Americans sleeping less than the recommended 7 hours/night, and sleep and wakefulness disorders impacting 50 to 70 million Americans. However, the biochemical mechanisms by which sleep loss contributes to metabolic disease are largely unknown, impeding the development of novel and effective countermeasures that target the negative metabolic consequences of sleep loss. Furthermore, it is unknown if the common and self-selected countermeasure of weekend recovery sleep attenuates the negative metabolic consequences of sleep loss. As such, I propose to identify the influence of insufficient sleep on mechanisms underlying metabolic dysregulation and determine the impact of “weekend recovery” sleep on these mechanisms. The proposed project will utilize metabolomics to analyze plasma samples from an ongoing in-laboratory study investigating insulin sensitivity and energy balance during insufficient sleep followed by weekend recovery sleep. Guided by my preliminary research efforts, I will use targeted and untargeted metabolomics approaches to identify metabolites and metabolic pathways impacted by insufficient sleep and weekend recovery sleep. Additionally, the untargeted discovery approach may identify potential “biomarkers” that change with sleep loss and “weekend recovery” sleep. My proposed findings will help inform future validation and sleep countermeasure investigations including testing at risk populations (i.e. obesity, pre-diabetes, shift-workers). This proposed F32-award is responsive to a key goal of the 2011 NIH Sleep Disorders Research Plan to “enable sleep and circadian research training to inform science in cross-cutting domains, accelerate the pace of discovery, and the translation of enhanced therapies from bench to bedside to community”, and is designed to advance my training in sleep and circadian physiology and metabolomics to strengthen my potential for a successful NIH Career Development K-award.