Social jetlag alters markers of exercise-induced mitochondrial adaptations in the heart

Social jetlag (SJL) represents the behavioral misalignment of sleep and wake times on work days and free days, and potently disrupts the circadian rhythm. SJL affects up to 70% of the population worldwide and is associated with increased risk for many cardiometabolic diseases. Animal models of acute SJL have shown disruption in locomotor activity and expression of clock genes in select tissues, its impact on the heart remains unclear. The purpose of this study was to investigate the effects of prolonged SJL (6 weeks), on activity rhythms, and the impact on exercise-induced adaptations in the heart. Male mice (n = 40, C57BL6) were assigned to a control light:dark (LD) cycle or SJL schedule (4-hour shift on weekends) for 6 weeks. Mice in each condition were further divided into voluntary exercise (EX) or sedentary (SED) groups. SJL resulted in significant shifts in the onset of physical activity in both sedentary (SJL-SED) and exercised (SJL-EX) mice on weekends, and exercise accelerated the speed of re-entrainment to the weekday schedule. Exercise induced myocardial hypertrophy in both CON-EX and SJL-EX groups. While there were no changes in mitochondrial content, SJL decreased expression of mitochondrial fusion proteins MFN1 and OPA1, and inhibited exercise-induced increases in MFN2. Taken together, these findings suggest that exercise hastens re-entrainment to the weekday schedule under SJL, but that SJL disrupts exercise-induced alterations to mitochondrial fusion/fission dynamics in the heart. Further investigation of cardiovascular function is warranted and will enable the development of strategies to prevent the effects of SJL on the heart.