Uncovering sleep and circadian mechanisms contributing to adverse metabolic health

揭示导致不良代谢健康的睡眠和昼夜节律机制

• 批准号: 10714191
• 负责人: Andrew William McHill
• 金额: $ 59.68万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714191
• 关键词: Accounting; Acute; American; Area; Automobile Driving; Behavior Therapy; Biological; Biology; Calories; Carbohydrates; Chronic; Circadian Dysregulation; Circadian desynchrony; Confounding Factors (Epidemiology); Consumption; Control Groups; Data; Desire for food; Diabetes Mellitus; Diet; Disease; Eating; Endocannabinoids; Energy Intake; Energy Metabolism; Epidemic; FAT gene; Fatty acid glycerol esters; Food; Food Access; Goals; Grapes; Health; Health Care Costs; Healthcare Systems; Hormones; Human; Hunger; Ice Cream; Impaired health; Impairment; Individual; Intake; Intervention; Laboratories; Measures; Metabolic; Metabolism; Modernization; Obesity; Outcome; Overweight; Participant; Pathway interactions; Pattern; Phase; Process; Protocols documentation; Randomized; Research; Research Priority; Risk; Rotation; Schedule; Sleep; Sleep Deprivation; Sleep Disorders; Societies; System; Testing; Time; United States; United States National Institutes of Health; Wakefulness; Weight Gain; Work; Yogurt; biological development; cardiometabolic risk; cardiometabolism; circadian; circadian biology; clinical translation; comorbidity; cost; design; endogenous cannabinoid system; energy balance; food quality; glucose tolerance; healthy weight; hedonic; impaired glucose tolerance; improved; insulin sensitivity; mortality; obese person; obesity risk; randomized, controlled study; shift work; sleep health; sleep onset; therapy development; translational study

Project Summary/Abstract Obesity and diabetes have reached epidemic proportions in modern society, with treatments and comorbidities costing billions of dollars in health care costs each year. Concurrent with increases in obesity and diabetes have been decreases in the amount of sleep millions of Americans obtain on a nightly basis. Though associations between short sleep and poor metabolic health are clear, exact mechanisms driving poor health are not well- understood. For example, inducing sleep restriction inherently results in a number of confounding variables, most notably circadian disruption, which also independently impairs health. It is thus difficult to develop targeted interventions without first identifying the individual and combined effects of chronic sleep restriction and circadian disruption on metabolism. The goal of this project is to systematically determine the influence of chronic sleep restriction and circadian disruption, both independently and in combination, on metabolic health. Our specific aims are to: 1) uncover the impact of chronic sleep restriction, circadian timing, and their combination on energy intake patterns; 2) determine the influence of chronic sleep restriction on food choice when there is equal opportunity to eat at all circadian times; and 3) uncover the impact of chronic sleep restriction, circadian timing, and their combination, on glucose tolerance. To accomplish our aims, we have designed a 14-day randomized- control mechanistic study in which participants will be either chronically sleep restricted or not while all activities are scheduled to occur evenly across all circadian phases on a 20-h “day” with ad libitum food access. We hypothesize that when individuals have equal opportunities to eat at all circadian times, they will 1) consume greater amounts of calories during the circadian evening independent of sleep condition, 2) sleep restriction will result in higher evening carbohydrate consumption, which will be associated with higher endocannabinoid concentrations, and 3) chronic sleep restriction will result in more impaired glucose tolerance after circadian disruption. These data will provide a fundamental understanding of how chronic sleep restriction and circadian disruption impacts metabolic health. Importantly, these data will have far-reaching implications, particularly in the development of interventions to promote healthy weight in not only individuals that are overweight/obese, but also those at risk for obesity who live on short sleep schedules and/or work on extended duration, rotating, or permanent nightshifts. This project also meets the following High-Priority Research Areas for future research in the NIH National Center on Sleep Disorders Research (NCSDR) plan. Goal 1: Elucidate the Sleep and Circadian Mechanisms Underlying Health and Disease, particularly in identifying sleep and circadian influences on the biology underlying obesity and cardiometabolic risk in humans and to better tailor interventions in clinical- translational studies, and Goal 2: Improve the Treatment of Sleep and Circadian Disorders and Reduce the Risks Associated with Sleep Deficiency and Circadian Misalignment, particularly in elucidating the relationship between circadian biology, sleep health, and the timing of food intake on cardiometabolic health and obesity.

项目摘要/摘要 肥胖和糖尿病在现代社会中达到了流行比例，治疗和合并症 每年耗资数十亿美元的医疗保健费用。同时增加肥胖和糖尿病的增加 他们在每晚获得数百万美国人获得的睡眠数量下降。虽然关联 在短睡眠和代谢不良之间是明确的，促进健康状况不佳的确切机制不是很好 理解齿。例如，诱导的睡眠限制本质上会导致许多混杂变量，大多数变量 特别是昼夜节律破坏，这也会独立损害健康。因此，很难开发目标 干预措施，没有先确定慢性睡眠限制和昼夜节律的个人和综合效果 新陈代谢的破坏。该项目的目的是系统地确定慢性睡眠的影响 限制和昼夜节律破坏，无论是独立还是结合了代谢健康。我们的具体 目的是：1）揭示慢性睡眠限制，昼夜节律的影响以及它们对能量的结合 进气模式； 2）确定慢性睡眠限制对食物选择的影响 有机会在所有昼夜节律时期吃饭； 3）发现慢性睡眠限制，昼夜节律的影响， 以及它们的结合，以葡萄糖耐受性。为了实现我们的目标，我们设计了一个14天的随机 - 控制机械研究，参与者在所有活动时都会长期受到限制或不限制睡眠 计划在20小时的“天”中均匀地在所有昼夜节律阶段均匀地发生，并随意获取食物。我们 假设，当个人在所有昼夜节律时期都有平等的进食机会时，他们将1）消费 在昼夜节律期间，更多的卡路里甚至与睡眠条件无关，2）睡眠限制将 导致较高的夜间碳水化合物消耗，这将与较高的内源性大麻素有关 浓度和3）慢性睡眠限制将导致昼夜节日后葡萄糖耐受性更大 破坏。这些数据将提供对慢性睡眠限制和昼夜节律的基本了解 破坏会影响代谢健康。重要的是，这些数据将具有深远的影响，特别是 开发干预措施以促进超重/肥胖的个人的健康体重的发展 而且那些处于短暂睡眠时间表和/或在延长持续时间，旋转， 或永久性夜班。该项目还符合以下供未来研究的高优先研究领域 在NIH国家睡眠障碍研究中心（NCSDR）计划中。目标1：阐明睡眠和 健康和疾病的昼夜节律机制，特别是在识别睡眠和昼夜节律的影响方面 关于人类的肥胖和心脏代谢风险的生物学，以更好地量身定制临床干预措施 翻译研究和目标2：改善睡眠和昼夜节律疾病的治疗并降低风险 与睡眠不足和昼夜节律的未对准有关，特别是在阐明 昼夜节律生物学，睡眠健康以及食物摄入量对心脏代谢健康和肥胖的时机。