Internal desynchrony of the hepatic circadian system with dissociated systemic rhythms in middle-aged mice under social jet lag-like conditions.

Social jet lag (SJL) leads to a misalignment between the circadian clock and social time. In this study, we investigated the effects of weekly shifts in light-dark (LD) conditions: two days per week with 6-h delayed LD cycles (simulating Saturday and Sunday). Core body temperature rhythms rapidly entrained to the delayed LD cycles on weekends, and these delayed rhythms persisted even after the LD cycle was advanced on Monday. In contrast, plasma corticosterone rhythms on Mondays did not show marked delays. In the livers of SJL mice on Monday, the expression rhythms of Per1, Per2, and Hsp70 were delayed compared to that in controls, whereas Rev-erbα expression rhythms remained comparable to those of the controls. The expression of lipid and glucose metabolism-related genes showed either delayed rhythms or no significant changes. In ex vivo experiments using liver slices, high-temperature stimulation induced Per2 and Hsp70 expression, while dexamethasone induced Per1 expression. High temperature and dexamethasone affected distinct sets of genes, and these responses were altered by weekly shifts in LD cycles. Overall, our findings indicate that weekly shifts in LD cycles induce internal desynchronization within the hepatic clock and metabolic pathways, possibly through uncoupling systemic circadian signals and gene-specific responses to stimuli.