Mechanisms addressing the causal relationships of sleep, circadian rhythms, and cardiometabolic health

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Modern lifestyles have led to short sleep and misalignment of behaviors to the endogenous circadian clock, which is governed by the light-dark cycle. The resulting deleterious effects on sleep quality and circadian rhythms have been associated with a plethora of chronic diseases that afflict a large portion of the population. Specifically, short sleep duration, poor quality sleep/sleep disorders, and circadian misalignment have been associated with an increased risk of obesity and cardiovascular disease. However, the causality of these associations and their underlying mechanisms have yet to be fully uncovered. In attempting to uncover the causal impact of insufficient sleep on obesity, our lab has shown that acute sleep restriction upregulates neuronal reward networks implicated in hedonic food consumption and results in higher intake of energy, particularly from fat, relative to adequate sleep. Others have also shown that these sleep manipulations drive late-night eating, which may then cause circadian misalignment. However, acute sleep restriction (<4 h of sleep/night for 5 nights) is not a typical behavior and we are now testing the impact of longer, milder forms of sleep restriction as well as prolonged circadian misalignment, on energy balance and cardiovascular disease risk. The main objective of this proposed research program is to elucidate the pathways by which sleep patterns and alignment of lifestyle behaviors, namely food consumption, activity, and sleep, to one another influence obesity and cardiovascular disease risk. We propose mechanistic clinical intervention studies in men and women that manipulate sleep and circadian rhythms as exposures on cardiometabolic risk factors. These randomized controlled interventions will include outcomes such as energy balance (measurements of food intake, energy expenditure, and body composition) and cardiovascular disease risk factors (cellular and systemic inflammation, immune function, glucose regulation, blood pressure). Men and women will be enrolled in equal numbers to assess whether the pathways that related poor sleep and circadian misalignment to cardiometabolic risk differ by sex. We plan to use the research flexibility afforded by this grant mechanism to expand collaborations with investigators in related and complementary fields of research, resulting in sharing of techniques and research paradigms between laboratories, train fellows and future investigators in the fields of sleep, circadian rhythms, and cardiometabolic health, and promote awareness of the importance of sleep and alignment of lifestyle behaviors to circadian clocks for optimal health.