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

ABSTRACT

Ozone (O3) 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 O3 exposure and the role of circadian rhythms in this process. C57BL/6 male mice were randomly assigned to O3 (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 O3 exposure to test. The results showed that hepatic circadian rhythm genes oscillated abnormally, mainly at zeitgeber time (ZT)8 and ZT20 after O3 exposure. Furthermore, detection of glycometabolism (metabolites, enzymes, and genes) revealed that O3 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. O3 exposure disrupted glycometabolism by increasing gluconeogenesis and decreasing glycolysis in mice liver. Finally, correlation analysis showed that the association between Bmal1 and O3-induced disruption of glycometabolism was the strongest. The findings emphasized the interaction between adverse outcomes of circadian rhythms and glycometabolism following O3 exposure.