Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver.

Ozone (O) is a key environmental factor for developing diabetes. Nevertheless, the underlying mechanisms remain unclear. This study aimed to investigate alterations of glycometabolism in mice after O exposure and the role of circadian rhythms in this process. C57BL/6 male mice were randomly assigned to O (0.5 ppm) or filtered air for four weeks (4 h/day). Then, hepatic tissues of mice were collected at 4 h intervals within 24 h after O exposure to test. The results showed that hepatic circadian rhythm genes oscillated abnormally, mainly at zeitgeber time (ZT)8 and ZT20 after O exposure. Furthermore, detection of glycometabolism (metabolites, enzymes, and genes) revealed that O caused change in the daily oscillations of glycometabolism. The serum glucose content decreased at ZT4 and ZT20, while hepatic glucose enhanced at ZT16 and ZT24(0). Both G6pc and Pck1, which are associated with hepatic gluconeogenesis, significantly increased at ZT20. O exposure disrupted glycometabolism by increasing gluconeogenesis and decreasing glycolysis in mice liver. Finally, correlation analysis showed that the association between Bmal1 and O-induced disruption of glycometabolism was the strongest. The findings emphasized the interaction between adverse outcomes of circadian rhythms and glycometabolism following O exposure.