Impact of circulating and tissue-specific lipids on vascular function and insulin sensitivity in chronic night shift workers - PROJECT SUMMARY/ABSTRACT There is growing recognition that timing of behaviors, such as eating, sleeping, and physical activity, have a significant impact on human health and disease risk. For example, when people are awake at the “wrong” time of the day (i.e. during the biological night), a mismatch occurs between behavior and biology, termed circadian misalignment. Shift workers experience repeated bouts of circadian misalignment and are at higher risk of cardiometabolic disease compared to people who work days. However, the mechanism(s) by which shift work and associated circadian misalignment increase disease risk are not clear. As a result, there have been few attempts to develop strategies to improve health in shift workers. Data from our group and others demonstrate that sleep and circadian disruption impair vascular endothelial function and insulin sensitivity, two important risk factors for future development of cardiovascular disease (CVD) and Type 2 diabetes (T2D), together termed cardiometabolic disease. Furthermore, sleep and circadian disruption increase lipids in plasma, including free fatty acids and ceramides, a class of lipids associated with cardiometabolic disease risk. We also find increases in specific lipid species in muscle, such as 1,2 diacylglycerols during circadian disruption, which can directly impair tissue-specific insulin signaling. Lastly, plasma lipids are elevated in shift workers; however, strategies that specifically target lipids in shift workers have not yet been conducted. Using a circadian-based eating model (time-restricted eating; TRE), we and others can consistently reduce lipids in circulation. TRE is also associated with reduced blood pressure and improved glucose homeostasis in healthy, lean adults during inpatient conditions of simulated night shift work. Thus, the clear next step is to translate this strategy to improve cardiometabolic disease risk in free-living shift workers who are neither young nor lean. The overall objective for this project is to improve the cardiometabolic health of free-living shift workers. Our central hypothesis is that eliminating food intake from the biological night (via TRE) will improve blood pressure, vascular function, insulin sensitivity, and glucose homeostasis in shift workers. To test our hypothesis, we will conduct a randomized crossover study (4-week TRE vs. 4- week controlled eating) in 50 non-rotating night shift workers (25F; >18y) with overweight or obesity. At the end of each outpatient condition, we will conduct a rigorous 2-day inpatient assessment to determine the impact of TRE and associated reductions in plasma and muscle lipids on blood pressure, vascular function, circulating markers of endothelial health, whole body and muscle-specific insulin sensitivity, whole body glucose homeostasis, and muscle insulin signaling. Successful completion of the proposed study will identify a targetable mechanism to counter impairments in vascular function and insulin sensitivity during shift work. The knowledge to be gained supports cost-effective programs to minimize CVD and T2D in populations at elevated risk, including anyone working nonstandard hours. These populations include workers in healthcare (nurses, doctors, paramedics), emergency services (military personnel, police, firefighters), security, transportation (pilots and truck drivers), manufacturing (our commercial partner), and hospitality, as well as the many individuals with sleep and circadian disorders.
