Food Timing to Mitigate Adverse Consequences of Night Work

减轻夜间工作不利后果的进食时间

基本信息

批准号：
10211816
负责人：
FRANK A SCHEER
金额：
$ 81.5万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10211816
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

项目摘要

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.

项目概要该项目的总体目标是确定将进餐时间限制在生物日是否表明对健康代谢标志物产生有益影响，这对弱势群体具有巨大的转化价值比如夜班工人。轮班工作会增加患糖尿病的风险，这不能完全解释为生活方式和社会经济地位的差异。我们已经证明了中央之间的错位夜班工人典型的生物钟和行为睡眠/觉醒和禁食/进食周期会导致不良的代谢变化，这可能有助于解释夜班工人患糖尿病风险增加的原因。动物数据显示出昼夜节律失调的类似不利代谢影响，并进一步表明，使昼夜节律正常化进食时间可以防止这些不良影响。在人类中，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减轻血糖调节作用昼夜节律失调的后果。然而，虽然我们未发表的初步数据显示了- 限制食物摄入量到生物日的原则，这具有有限的转化价值，因为进餐时间需要在睡眠期间给予，这对于长期轮班工人来说显然是不可取的。因此，当前应用中要解决的一个关键差距是测试是否限制进餐时间到生物日 - 不干扰睡眠 - 可以减轻昼夜节律的不利代谢影响与同一个人在夜间工作期间安排膳食相比，存在偏差转变（具体目标 1）。为了实现这一目标，我们将在实验室模拟真实的夜班用餐情况安排在生物之夜（控制方案）或仅限于生物日的膳食（干预方案）使用高度控制的、受试者内的、随机的、交叉设计。此外，常见的遗传褪黑激素受体基因 MTNR1B 的变异会增加糖尿病风险，在昼夜节律中发挥关键作用褪黑激素和葡萄糖调节的组织。因此，我们还将检查常见的 MTNR1B 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，肠道微生物群在代谢健康中发挥着关键作用，其破坏已在昼夜节律下观察到错位。因此，我们计划测试将进餐时间限制在生物日是否可以减轻其影响破坏（具体目标 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不良代谢影响的潜在机制昼夜节律失调，将有助于开发基于夜班用餐时间的新颖干预措施工作和其他昼夜节律紊乱。