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 However, while our unpublished preliminary data show a proof-of-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.