Uncovering sleep and circadian mechanisms contributing to adverse metabolic health

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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.