Simulated Night- Shift Schedule Disrupts the Plasma Lipidome and Reveals Early Markers of Cardiovascular Disease Risk

The circadian system coordinates daily rhythms in lipid metabolism, storage and utilization. Disruptions of internal circadian rhythms due to altered sleep/wake schedules, such as in night-shift work, have been implicated in increased risk of cardiovascular disease and metabolic disorders. To determine the impact of a night-shift schedule on the human blood plasma lipidome, an in-laboratory simulated shift work study was conducted.Fourteen healthy young adults were assigned to 3 days of either a simulated day or night-shift schedule, followed by a 24-h constant routine protocol with fixed environmental conditions, hourly isocaloric snacks, and constant wakefulness to investigate endogenous circadian rhythms. Blood plasma samples collected at 3-h intervals were subjected to untargeted lipidomics analysis.More than 400 lipids were identified and quantified across 21 subclasses. Focusing on lipids with low between-subject variation per shift condition, alterations in the circulating plasma lipidome revealed generally increased mean triglyceride levels and decreased mean phospholipid levels after night-shift relative to day-shift. The circadian rhythms of triglycerides containing odd chain fatty acids peaked earlier during constant routine after night-shift. Regardless of shift condition, triglycerides tended to either peak or be depleted at 16:30 h, with chain-specific differences associated with the direction of change.The simulated night-shift schedule was associated with altered temporal patterns in the lipidome. This may be premorbid to the elevated cardiovascular risk that has been found epidemiologically in night-shift workers.