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.

项目总结/摘要 肥胖和糖尿病在现代社会已经达到流行病的比例，治疗和合并症 每年花费数十亿美元的医疗费用。与肥胖和糖尿病的增加同时， 数以百万计的美国人每晚获得的睡眠量减少了。虽然协会 睡眠不足和代谢不佳之间的联系是明确的，导致健康不佳的确切机制还不清楚- 明白例如，诱导睡眠限制固有地导致许多混淆变量，大多数 特别是昼夜节律紊乱，这也独立地损害健康。因此，很难有针对性地开发 没有首先确定慢性睡眠限制和昼夜节律的个体和综合影响的干预措施 破坏新陈代谢。这个项目的目标是系统地确定慢性睡眠的影响 限制和昼夜节律紊乱，无论是独立的还是组合的，对代谢健康的影响。我们的具体 目的是：1）揭示慢性睡眠限制，昼夜节律时间以及它们的组合对能量的影响 摄入模式; 2）确定慢性睡眠限制对食物选择的影响，当有相同的 在所有昼夜节律时间进食的机会;以及3）揭示慢性睡眠限制，昼夜节律时间， 以及它们的组合对葡萄糖耐量的影响。为了实现我们的目标，我们设计了一个14天的随机- 控制机制研究，参与者将长期睡眠限制或没有，而所有活动 被安排在20小时“一天”的所有昼夜节律阶段中均匀发生，自由进食。我们 我假设，当个体在所有昼夜节律时间都有平等的机会进食时，他们将1）消费 更多的热量在昼夜节律晚上独立于睡眠条件，2）睡眠限制将 导致更高的晚间碳水化合物消耗，这将与更高的内源性大麻素有关 3）慢性睡眠限制将导致昼夜节律后更多的葡萄糖耐量受损 破坏这些数据将提供一个基本的了解，慢性睡眠限制和昼夜节律 破坏影响代谢健康。重要的是，这些数据将产生深远的影响，特别是在 发展干预措施，不仅促进超重/肥胖个体的健康体重， 还有那些睡眠时间短和/或工作时间长，轮班， 或者长期上夜班该项目还满足以下高优先级研究领域的未来研究 国家睡眠障碍研究中心（National Center on Sleep Disorders Research，NCSDR）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影响方面 研究人类肥胖和心脏代谢风险的生物学基础，并更好地调整临床干预措施， 目标2：改善睡眠和昼夜节律紊乱的治疗并降低风险 与睡眠不足和昼夜失调有关，特别是在阐明 昼夜节律生物学、睡眠健康和食物摄入时间对心脏代谢健康和肥胖的影响。