Time-restricted feeding to mitigate metabolic impairments during circadian misalignment

限时喂养可减轻昼夜节律失调期间的代谢损伤

基本信息

批准号：
10653934
负责人：
Josiane Broussard
金额：
$ 61.51万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-12 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10653934
关键词：
Abdomen Achievement Acute Adult Attenuated Behavior Behavioral Biological Biopsy Blood specimen Chronic Disease Circadian Dysregulation Circadian Rhythms Circadian desynchrony Consumption Cross-Over Studies Data Development Diabetes Mellitus Diet Disease Management Eating Employee Energy Intake Environmental Risk Factor Fatty acid glycerol esters Gene Expression Genes Glucose Glucose Clamp Glycolysis Goals Healthcare Homeostasis Hour Hyperinsulinism Impairment Individual Inpatients Insulin Resistance Intervention Jet Lag Syndrome Knowledge Laboratories Light Link Lipids Medical Medical Residency Metabolic Metabolic Diseases Military Personnel Modernization Muscle Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Nurses Paramedical Personnel Persons Physiology Pilot Projects Plasma Police Population Populations at Risk Protocols documentation Quantitative Reverse Transcriptase PCR Randomized Risk Risk Factors Rotation Sampling Savings Schedule Sleep Sleep Deprivation Sleep Disorders Sleep disturbances Societies System Testing Time Time-restricted feeding Weight Gain Woman Work awake circadian clinically relevant combat cost effective diabetes risk disorder prevention disorder risk emergency service responder experience fatty acid metabolism fire fighter improved in vivo insulin sensitivity intrahepatic men novel obesity development obesity risk prevent programs risk mitigation shift work transcriptome sequencing translatable strategy

项目摘要

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.

项目概要/摘要晚上、夜班或轮班（即“非标准”工作时间）工作的人占五分之一与人类相比，美国员工患 2 型糖尿病 (T2D) 的可能性高出 44%，令人震惊昼夜节律失调是增加白班风险的一种机制。肥胖和糖尿病在非标准工作时间的人群中非常普遍，而且往往是不可避免的现代 24 小时社会（例如轮班工作、长时间工作、时差、住院医师、紧急救援人员、军事人员、夏令时变化等）。与胰岛素抵抗、能量摄入增加、体重增加以及全身、腹部和肌肉增加有关肝内脂肪含量，但在确定策略或对策方面的尝试有限防止这种干扰对相当大一部分人群的 T2D 风险产生影响。因此，我们的长期目标是确定和制定有效的行为对策对抗与睡眠和昼夜节律紊乱相关的代谢疾病风险增加该项目的总体目标是测试限时喂养的影响。一天中的 7 小时作为与以下相关的代谢损伤的非侵入性对策我们的中心假设是，白天限时喂食可以防止昼夜节律失调。与消耗能量的情况相比，昼夜节律失调期间的代谢障碍拟议项目的基本原理是定义一个非侵入性的、可扩展的。针对昼夜节律失调的可行对策可以降低肥胖和 T2D 的风险。为了检验我们的总体假设，将使用随机交叉研究和严格的住院饮食，我们将确定 32 名健康男性和女性的活动和光控方案的影响。 1) 肌肉组织胰岛素敏感性和基因表达的昼夜节律失调期间限制进食； 2) 肌肉组织脂质积累和循环夜间 FFA 和葡萄糖浓度。这项研究的结果代表了转化昼夜节律和通过识别和测试昼夜节律失调的对策来实现代谢生理学。我们提出的目标可能会导致制定新的慢性病预防干预策略所获得的知识有可能支持具有成本效益的计划。告知我们的医疗保健方法，以预防有这些疾病风险的人群，例如轮班工人、有睡眠障碍的人以及任何在白天以外进食的人。