Food Timing to Mitigate Adverse Consequences of Night Work

减轻夜间工作不利后果的进食时间

• 批准号: 10434754
• 负责人: FRANK A SCHEER
• 金额: $ 79.53万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10434754
• 关键词: Address; Adverse effects; Behavioral; Beta Cell; Biological; Body Weight; Cell physiology; Chronic; Circadian Rhythms; Circadian desynchrony; Crossover Design; Data; Development; Dietary Intervention; Eating; Endotoxins; Fasting; Food; Glucose Intolerance; Goals; Health; Human; Individual; Inflammation; Insulin; Intervention; Intestinal permeability; Jet Lag Syndrome; Laboratories; Life Style; Link; Measures; Melatonin; Melatonin Receptors; Metabolic; Metabolic Marker; Metabolic dysfunction; Middle Insomnia; Modeling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oral; Oranges; Play; Populations at Risk; Protocols documentation; Randomized; Receptor Gene; Research; Research Design; Risk; Role; Saliva; Schedule; Serum Markers; Shapes; Signal Transduction; Sleep; Sleep Wake Cycle; Sleep disturbances; Socioeconomic Status; Structure; Testing; Time; Variant; Vulnerable Populations; adverse outcome; animal data; arm; base; circadian; circadian pacemaker; circadian regulation; design; diabetes risk; dysbiosis; evidence base; experimental study; feeding; genetic variant; glucose tolerance; gut microbiota; impaired glucose tolerance; improved; inflammatory marker; insulin secretion; insulin sensitivity; intestinal barrier; metabolomics; microbial community; microbiota; microbiota transplantation; novel; prevent; receptor expression; risk variant; shift work; socioeconomics; stool sample; systemic inflammatory response; targeted treatment; trait

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.

项目摘要 这个项目的主要目标是确定是否限制用餐时间的生物日显示， 对健康代谢指标的有益影响，对弱势群体具有巨大的转化价值 例如夜班工人。轮班工作增加了患糖尿病的风险，这不能完全解释为 生活方式和社会经济地位的差异。我们已经证明，中央和中央之间的错位 昼夜节律钟和行为睡眠/觉醒和禁食/喂养周期，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者糖尿病风险增加的原因。动物数据 显示了昼夜节律失调的类似不利代谢作用，并进一步显示了使昼夜节律正常化 进食时机可以防止这些不良影响。在人类中，我们从严格控制的 昼夜节律实验表明，将进餐时间限制在生物日可以减轻血糖调节 生理失调的后果然而，尽管我们未公布的初步数据显示， 根据将食物摄入量限制在生物日的原则，这具有有限的转化价值，因为用餐时间 要求在睡眠期间服用，这显然不适合长期轮班的工人。 因此，在当前应用中将解决的一个关键差距是测试是否限制进餐时间 在不干扰睡眠的情况下， 与同一个人在夜间工作时安排用餐时间相比， 具体目标1（Specific Aim 1）为了实现这一目标，我们将在实验室模拟现实的夜班与膳食 安排在生物学夜晚（控制方案）或限制在生物学白天进餐（干预 方案），采用高度对照、受试者内、随机、交叉设计。此外，常见的遗传 褪黑激素受体基因MTNR 1B的变体赋予糖尿病风险，在昼夜节律中起着关键作用。 褪黑激素和葡萄糖调节的组织。因此，我们还将研究常见的MTNR 1B是否 遗传变异调节进餐时间对血糖调节的影响（具体目标2）。最后，肠 微生物群在代谢健康中起着关键作用，并且在昼夜节律下观察到其破坏 未对准。因此，我们计划测试将进餐时间限制在生物日是否可以减轻其 破坏（具体目标3），这可能会减轻昼夜节律的有害代谢后果 未对准。这项研究将有助于揭示潜在的机制，潜在的不良代谢作用， 昼夜节律失调，并将有助于开发基于夜班用餐时间的新干预措施 工作和其他昼夜节律紊乱。