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

Abstract

Jennifer E Kyle,1 Lisa M Bramer,1 Daniel Claborne,2 Kelly G Stratton,1 Kent J Bloodsworth,1 Justin G Teeguarden,1,3 Shobhan Gaddameedhi,4 Thomas O Metz,1 Hans PA Van Dongen5,6 1Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA, 99352, USA; 2Computing and Analytics Division, National Security Directorate, PNNL, Richland, WA, 99352, USA; 3Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331, USA; 4Department of Biological Sciences and Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA; 5Sleep and Performance Research Center, Washington State University, Spokane, WA, 99202, USA; 6Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, 99202, USACorrespondence: Jennifer E Kyle, Pacific Northwest National Laboratory, PO Box 999, MSIN: K8-98, Richland, WA, 99352, USA, Tel [phone], Fax [phone], Email [email protected]: 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.Methods: 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.Results: 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.Discussion: 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.Keywords: lipidomics, mass spectrometry, circadian disruption, working time arrangements, cardiovascular health, triglycerides

Keywords

• lipidomics | mass spectrometry | circadian disruption | working time arrangements | cardiovascular health | triglycerides