Time-of-day And Sex-dependent Effects Of Exercise On Cardiometabolic Health In Mice With Social Jetlag

Physiology has adapted to function on a 24 hour time scale, referred to as the circadian rhythm. Operating outside of this time scale leads to circadian rhythm disruption, which invariably leads to pathological outcomes. Social jetlag (SJL), a common form of circadian rhythm disruption, occurs when an individual’s sleep/wake schedule differs throughout the week (i.e. – staying up late on the weekends), and has been associated with obesity and cardiovascular disease. Exercise is a potential intervention to prevent SJL-induced impairments, but the time of day at which exercise is most effective is unknown. PURPOSE: Determine if early or late phase exercise is capable of preventing SJL-induced impairments in cardiometabolic health in mice. METHODS: Male and female mice (C57BL6, ~10 weeks of age; n = 5-10/group) were allocated to either Control (CON; strict 12:12 LD), or SJL conditions (4 hour shift in LD every weekend). Mice in each group were further divided into Sedentary (SED), Early Active Phase (EAP; wheel access from ZT12-18), or Late Active Phase (LAP; wheel access from ZT18-24) groups, for 10 weeks. Body weight (BW), glucose tolerance tests (GTT), and graded exercise tests (GXT) were performed to evaluate cardiovascular fitness ane metabolic health at baseline and after 10 weeks. 24-hour patterns in food and body weight were recorded. RESULTS: Exercise prevented body weight gain in males, but not females, independent of time. SJL increased the GTT area under the curve in male mice, which was partially reduced by exercise (EX x SJL interaction; p CONCLUSION: SJL elicits negative effects on metabolic health, particularly glucose tolerance, which can be ameliorated by exercise. The effects of SJL are sex-dependent, and the adaptations to exercise are also moderated by sex. SJL-induced alterations in feeding and activity rhythms likely underpins pathological effects.