Time-restricted feeding to mitigate metabolic impairments during circadian misalignment

项目摘要/摘要 夜班、夜班或轮班工作的人(即非标准工作时间)占五分之一 与美国人相比，美国员工患2型糖尿病(T2D)的可能性高出44%，令人震惊 都是标准的日班工作。昼夜节律失调是一种增加高血压风险的机制 肥胖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、住院医师、急救人员、 军事人员、夏令时更改等)。睡眠和昼夜节律的中断 与胰岛素抵抗、能量摄入增加、体重增加以及全身、腹部和 肝内脂肪含量，但确定策略或对策的尝试有限 在相当大比例的人群中防止此类中断对T2D风险的影响。 因此，我们的长期目标是确定和开发有效的行为对策，以 与睡眠和昼夜节律紊乱相关的代谢性疾病风险增加作斗争时， 行为是不可避免的。这个项目的总体目标是测试限时喂养的影响 作为一种非侵入性对策，以应对与以下相关的代谢损害 昼夜节律失调。我们的中心假设是，在白天有时间限制摄食将防止 昼夜节律失调期间的代谢损伤与能量消耗状态的比较 不分昼夜。提议的项目的基本原理是定义一种非侵入性、可扩展的 可行的昼夜节律失调对策可以降低肥胖和T2D的风险。 为了检验我们的整体假设，将使用随机交叉研究和严格的住院患者饮食-， 32名健康男性和女性的活动和光控方案。我们将确定时间的影响- 昼夜节律失调时的限食：1)肌肉组织的胰岛素敏感性和基因表达； (2)肌肉组织脂肪堆积和夜间循环FFA和血糖浓度。 这项研究的发现代表了翻译昼夜节律和 新陈代谢生理学通过识别和测试针对昼夜节律失调的对策。取得的成就 我们提出的目标可能会导致开发新的慢性病预防干预策略 和管理。将获得的知识提供了支持具有成本效益的计划的潜力，这些计划可能 告知我们在这些疾病的高危人群中预防代谢性疾病的医疗保健方法 作为轮班工作人员、有睡眠障碍的人以及任何在白天以外吃东西的人。

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.