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Updated: Jul 15, 2025
Evaluation of Hepatic Glucose Production in a Polycystic Ovary Syndrome Mouse Model
Published on: March 5, 2022
Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver
Yaru Zhang1, Zhipeng Yan1, Nan Nan1
1College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.
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.
Insights
Ozone exposure disrupts the body's internal clock and glucose metabolism. This study reveals how ozone impacts liver function and highlights the link between circadian rhythm disruption and metabolic changes.
Area of Science:
- Environmental Health
- Metabolomics
- Chronobiology
Background:
- Ozone (O3) is an environmental factor linked to diabetes development.
- The precise mechanisms by which ozone affects metabolic processes remain largely unknown.
- Circadian rhythms play a crucial role in regulating physiological functions, including metabolism.
Purpose of the Study:
- To investigate the impact of ozone exposure on glycometabolism in mice.
- To explore the role of circadian rhythms in ozone-induced metabolic alterations.
- To elucidate the specific changes in hepatic glucose metabolism following ozone exposure.
Main Methods:
- C57BL/6 male mice were exposed to ozone (0.5 ppm) or filtered air for four weeks.
- Hepatic tissues were collected at 4-hour intervals over 24 hours post-exposure.
- Analysis included circadian rhythm genes, glycometabolism markers (metabolites, enzymes, genes), and correlation analysis.
Main Results:
- Ozone exposure led to abnormal oscillations in hepatic circadian rhythm genes, particularly at ZT8 and ZT20.
- Daily patterns of glycometabolism were altered, with decreased serum glucose and increased hepatic glucose at specific times.
- Key gluconeogenesis genes (G6pc, Pck1) increased at ZT20, indicating enhanced glucose production.
- Ozone exposure promoted hepatic gluconeogenesis and inhibited glycolysis.
Conclusions:
- Ozone exposure disrupts the normal circadian rhythm of glycometabolism in the liver.
- The study identified a strong association between the circadian rhythm gene Bmal1 and ozone-induced metabolic disruption.
- Findings underscore the intricate interaction between circadian rhythm disturbances and metabolic dysfunction following ozone exposure.
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