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

• 批准号: 10440376
• 负责人: Josiane Broussard
• 金额: $ 62.85万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 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/10440376
• 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; Impairment; Individual; Inpatients; Insulin Resistance; Intervention; Jet Lag Syndrome; Knowledge; Laboratories; Lead; 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; 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; shift work; transcriptome sequencing; translatable strategy

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.

项目摘要/摘要 上班，夜间或旋转班次的人（即“非标准”工作时间）代表五分之一。 与人相比 谁在做标准的日常转变。 在工作时间的人中，肥胖和糖尿病是非标准的，并且非常普遍，并且通常不可避免 现代24小时的社会（例如，轮班工作，漫长的工作时间，喷气滞后，医疗居留权，紧急响应者， 军事人员，日光储蓄时间的变化等）。 与胰岛素抵抗，能量摄入增加，体重增加以及总体，腹部和 肝内脂肪含量，但这些尝试是有限的尝试，试图识别策略或对策 防止这种讨论对大量人群中T2D风险的影响。 因此，我们的长期目标是确定和发展有效的行为对策 与睡眠和昼夜节律中断相关的代谢射击风险增加的风险增加 行为不可避免。 当天的7h时期是与与之相关的代谢障碍的无创反应 昼夜节律错位是我们的中心假设 与消耗能量的情况相比 整个黑夜。 对昼夜节律未对准的对策可能会遇到肥胖和T2D的风险。 为了检验我们的总体假设，将使用严格的住院饮食， 32名健康男性和女性的活动和光控制方案。 在昼夜节律不一致期间，肌肉组织胰岛素敏感性和基因表达限制； 2）肌肉组织脂质积累和循环的肿瘤FFA和葡萄糖浓度。 研究研究的结果代表了转化昼夜节律领域的关键进步 通过识别和测试昼夜节律未对准的对策，代谢生理。 我们提出的目标可能导致导致开发用于预防慢性疾病的新干预策略 和管理的知识。 告知我们的医疗保健方法，以预防代谢疾病的普及，处于这些疾病的风险中 作为班次的工人，患有睡眠障碍的人以及任何在白天外面用餐的人。