Food Timing to Mitigate Adverse Consequences of Night Work

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Project Summary The broad goal of this project is to determine whether restricting meal timing to the biological day shows beneficial effects on metabolic markers of health, which holds great translational value for vulnerable populations such as night shift workers. Shift work increases the risk for diabetes, which cannot be fully explained by differences in life style and socioeconomic status. We have demonstrated that misalignment between the central circadian clock and the behavioral sleep/wake and fasting/feeding cycle, typical in night shift workers, leads to adverse metabolic changes, which may help explain the increased diabetes risk in night workers. Animal data show similar adverse metabolic effects of circadian misalignment and further show that normalizing the circadian food timing prevents these adverse effects. In humans, our preliminary data from a stringently-controlled circadian experiment suggest that restricting meal timing to the biological day can mitigate the glucoregulatory consequences of circadian misalignment. However, while our unpublished preliminary data show a proof-of- principle for restricting food intake to the biological day, this has limited translational value, because meal times were required to be given during the sleep episodes, which is clearly not advisable to chronic shift workers. Therefore, a key gap that will be addressed in the current application is testing whether restriction of meal timing to the biological day - without disrupting sleep - can mitigate the adverse metabolic effects of circadian misalignment, as compared to when the same individuals have their meals scheduled during their night work shift (Specific Aim 1). To achieve this goal, we will simulate realistic night shifts in laboratory with meals scheduled during the biological night (control protocol) or with meals restricted to the biological day (intervention protocol) using a highly-controlled, within-subject, randomized, crossover design. In addition, common genetic variants in the melatonin receptor gene, MTNR1B, confers diabetes risk, playing a key role in the circadian organization of melatonin and glucoregulation. Thus, we will also examine whether the common MTNR1B genetic variants modulate the effects of meal timing on glucoregulation (Specific Aim 2). Last, intestinal microbiota plays a key role in metabolic health, and its disruption has been observed under circadian misalignment. Therefore, we plan to test whether restricting meal timing to the biological day can mitigate its disruption (Specific Aim 3), which may alleviate the deleterious metabolic consequences of circadian misalignment. This study will help uncover potential mechanisms underlying the adverse metabolic effects of circadian misalignment and will aid in the development of novel interventions based on meal timing for night shift work and other circadian rhythm disturbances.