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：
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
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/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

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.

项目摘要该项目的广泛目标是确定是否将膳食时间限制为生物日对健康代谢标记的有益影响，这对弱势群体具有巨大的翻译价值例如夜班工人。轮班工作增加了糖尿病的风险，不能完全解释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昼夜节时间和行为睡眠/唤醒和禁食/喂养周期（典型的夜班工人）导致不良代谢变化，这可能有助于解释夜间工人的糖尿病风险增加。动物数据显示出类似的不良代谢作用的昼夜节律未对准，并进一步表明使昼夜节律正常化食物时机阻止了这些不利影响。在人类中，我们从严格控制的初步数据昼夜节律实验表明，限制饮食时间到生物日可以减轻葡萄糖调节昼夜节律错位的后果。但是，尽管我们未发表的初步数据显示了将食物摄入量限制为生物学日的原则，这是有限的翻译价值，因为用餐时间需要在睡眠情节中给出，这显然不建议慢性转变工人。因此，当前申请中将解决的关键差距是测试饮食时机是否限制到生物学日 - 不破坏睡眠 - 可以减轻昼夜节律的不良代谢影响与同一个人在夜间工作期间安排餐点相比，错位不对班次（特定目标1）。为了实现这一目标，我们将模拟用餐实验室的现实夜班计划在生物之夜（控制方案）或限制在生物日的餐点（干预）协议）使用高度控制的，受试者内随机，交叉设计。另外，普通遗传褪黑激素受体基因MTNR1B中的变体赋予糖尿病风险，在昼夜节律中起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是否遗传变异调节粉末时间对葡萄糖调节的影响（特定目标2）。最后，肠道微生物群在代谢健康中起关键作用，并且在昼夜节律下观察到了它的破坏错位。因此，我们计划测试将进餐时间限制为生物日的时间是否可以减轻其破坏（特定目标3），这可能减轻昼夜节律的有害代谢后果错位。这项研究将有助于发现对不良代谢作用的潜在机制昼夜节律的未对准，将有助于基于夜班的餐时机制定新颖的干预措施工作和其他昼夜节律障碍。