Time-restricted feeding to mitigate metabolic impairments during circadian misalignment

项目总结/摘要 上晚班、夜班或轮班（即“非标准”工作时间）的人占五分之一 美国2型糖尿病（T2 D）的发病率比普通人高出44%， 他们上的是标准的白班昼夜节律失调是一种机制，建议增加的风险， 肥胖症和糖尿病在非标准工作时间的人中非常普遍，而且在 现代，24小时社会（例如轮班工作，长时间工作，时差，医疗住院，紧急反应， 军事人员、夏令时变化等）。睡眠和昼夜节律的紊乱 与胰岛素抵抗、能量摄入增加、体重增加和全身、腹部和 肝内脂肪含量，但在确定策略或对策方面的尝试有限， 防止这种中断对相当大比例的人群中T2 D风险的影响。 因此，我们的长期目标是确定和制定有效的行为对策， 与睡眠和昼夜节律紊乱相关的代谢疾病的风险增加作斗争， 行为不可避免。本项目的总体目标是测试限时喂养的影响 作为一种非侵入性的对策，与代谢障碍相关的 昼夜节律失调我们的中心假设是，限制时间喂养到白天将防止 与消耗能量的情况相比， 在白天和黑夜。提出该项目的理由是，定义一个非侵入性的，可扩展的 对昼夜节律失调采取可行的对策可以降低肥胖和2型糖尿病的风险。 为了检验我们的总体假设，将使用一项随机交叉研究，采用严格的住院饮食， 活动和光控制协议在32名健康男性和女性。我们将确定时间的影响- 昼夜节律失调期间限制进食对1）肌肉组织胰岛素敏感性和基因表达的影响; 和2）肌肉组织脂质积聚和循环夜间FFA和葡萄糖浓度。 这项研究的发现代表了翻译昼夜节律和 代谢生理学通过识别和测试昼夜节律失调的对策。实现 我们提出的目标可能会导致新的慢性病预防干预策略的发展 和管理获得的知识提供了支持具有成本效益的方案的潜力， 告知我们的医疗保健方法，以预防处于这些疾病风险中的人群的代谢性疾病， 轮班工作者、睡眠障碍者和在白天以外时间进食的人。

PROJECT SUMMARY/ABSTRACT People who work evening, night or rotating shifts (i.e. “nonstandard” work hours) represent one in five U.S. employees and are alarmingly 44% more likely to develop Type 2 diabetes (T2D) compared to people who work standard day shifts. Circadian misalignment is one mechanism suggested to increases the risk of obesity and diabetes in people who work non-standard hours, and is highly prevalent and often unavoidable in modern, 24-hour society (e.g. shift work, long work hours, jet lag, medical residency, emergency responders, military personnel, Daylight Savings Time changes, etc). Disruptions in sleep and circadian rhythms have been linked to insulin resistance, increased energy intake, weight gain, and increased total body, abdominal and intrahepatic fat content, yet there have been limited attempts at identifying strategies or countermeasures to prevent the impact of such disruption on T2D risk in a sizeable proportion of the population. Therefore, our long-term goal is to identify and develop effective, behavioral countermeasures to combat the increased risk for metabolic diseases associated with sleep and circadian disruption when these behaviors are unavoidable. The overall objective for this project is to test the impact of time-restricted feeding to a 7h period in the day as a noninvasive countermeasure to the metabolic impairments associated with circadian misalignment. Our central hypothesis is that time-restricted feeding to the daytime period will prevent metabolic impairments during circadian misalignment compared to a condition where energy is consumed throughout the day and night. The rationale for the proposed project is that defining a non-invasive, scalable and feasible countermeasure to circadian misalignment could mitigate the risk of obesity and T2D. To test our overall hypothesis, will use a randomized crossover study with a rigorous inpatient diet-, activity and light-controlled protocol in 32 healthy men and women. We will determine the impact of time- restricted feeding during circadian misalignment on 1) muscle tissue insulin sensitivity and gene expression; and 2) muscle tissue lipid accumulation and circulating nocturnal FFA and glucose concentrations. Findings from this study represent a critical advancement in the fields of translational circadian and metabolic physiology by identifying and testing a countermeasure to circadian misalignment. Achievement of our proposed aims could lead to the development of new intervention strategies for chronic disease prevention and management. The knowledge to be gained offers the potential to support cost-effective programs that may inform our healthcare approach to metabolic disease prevention in populations at risk for these diseases such as shift workers, individuals with sleep disorders and anyone who eats outside of daytime hours.