Food Timing to Mitigate Adverse Consequences of Night Work

项目摘要 这个项目的主要目标是确定是否将进餐时间限制在生物日节目中 对健康代谢标记物的有益影响，这对脆弱人群具有很大的翻译价值 比如上夜班的工人。倒班工作增加了患糖尿病的风险，这不能用以下方式完全解释 生活方式和社会经济地位的差异。我们已经证明，中央和地方政府之间的不协调 生物钟和行为睡眠/醒来和禁食/进食周期，这在夜班工人中是典型的，导致 不利的代谢变化，这可能有助于解释夜间工作人员患糖尿病风险增加的原因。动物数据 表现出类似的昼夜节律失调的不利代谢影响，并进一步表明，使昼夜节律正常化 适时进食可防止这些不良影响。在人类身上，我们的初步数据来自严格控制的 昼夜节律实验表明，将进餐时间限制在生物日可以缓解血糖调节 昼夜节律失调的后果。然而，尽管我们未公布的初步数据表明- 将食物摄入量限制在生物日的原则，这一原则具有有限的翻译价值，因为用餐时间 要求在睡眠期间服用，这对长期轮班的工人显然是不可取的。 因此，将在当前应用中解决的一个关键差距是测试是否限制用餐时间 到生物日--不干扰睡眠--可以减轻昼夜节律对新陈代谢的不利影响 不协调，与相同的人在夜间工作时安排用餐时间相比 Shift(特定目标1)。为了实现这一目标，我们将模拟真实的实验室夜班和用餐 安排在生物夜间(控制方案)或在生物白天限制用餐(干预 协议)使用高度受控、受试者内、随机、交叉设计。此外，常见的基因 褪黑素受体基因MTNR1B的变异增加了患糖尿病的风险，在昼夜节律中起着关键作用 褪黑素的组织和糖调节。因此，我们还将审查共同的MTNR1B是否 基因变异调节进餐时间对血糖调节的影响(特定目标2)。最后，肠道 微生物区系在代谢健康中起着关键作用，在昼夜节律下观察到了微生物区系的破坏。 错位。因此，我们计划测试将进餐时间限制在生物日是否可以缓解其 干扰(特定目标3)，这可能会减轻昼夜节律的有害代谢后果 错位。这项研究将有助于揭示潜在的机制，潜在的不利代谢影响 昼夜节律失调，并将有助于开发基于夜班进餐时间的新干预措施 工作和其他昼夜节律紊乱。

Project Summary The broad goal of this project is to determine whether restricting meal timing to the biological day shows beneficial effects on metabolic markers of health, which holds great translational value for vulnerable populations such as night shift workers. Shift work increases the risk for diabetes, which cannot be fully explained by differences in life style and socioeconomic status. We have demonstrated that misalignment between the central circadian clock and the behavioral sleep/wake and fasting/feeding cycle, typical in night shift workers, leads to adverse metabolic changes, which may help explain the increased diabetes risk in night workers. Animal data show similar adverse metabolic effects of circadian misalignment and further show that normalizing the circadian food timing prevents these adverse effects. In humans, our preliminary data from a stringently-controlled circadian experiment suggest that restricting meal timing to the biological day can mitigate the glucoregulatory consequences of circadian misalignment. However, while our unpublished preliminary data show a proof-of- principle for restricting food intake to the biological day, this has limited translational value, because meal times were required to be given during the sleep episodes, which is clearly not advisable to chronic shift workers. Therefore, a key gap that will be addressed in the current application is testing whether restriction of meal timing to the biological day - without disrupting sleep - can mitigate the adverse metabolic effects of circadian misalignment, as compared to when the same individuals have their meals scheduled during their night work shift (Specific Aim 1). To achieve this goal, we will simulate realistic night shifts in laboratory with meals scheduled during the biological night (control protocol) or with meals restricted to the biological day (intervention protocol) using a highly-controlled, within-subject, randomized, crossover design. In addition, common genetic variants in the melatonin receptor gene, MTNR1B, confers diabetes risk, playing a key role in the circadian organization of melatonin and glucoregulation. Thus, we will also examine whether the common MTNR1B genetic variants modulate the effects of meal timing on glucoregulation (Specific Aim 2). Last, intestinal microbiota plays a key role in metabolic health, and its disruption has been observed under circadian misalignment. Therefore, we plan to test whether restricting meal timing to the biological day can mitigate its disruption (Specific Aim 3), which may alleviate the deleterious metabolic consequences of circadian misalignment. This study will help uncover potential mechanisms underlying the adverse metabolic effects of circadian misalignment and will aid in the development of novel interventions based on meal timing for night shift work and other circadian rhythm disturbances.