1. Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice.
- Author
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Ding, Shibin, Yuan, Chunyan, Si, Bingjie, Wang, Mengruo, Da, Shuyan, Bai, Lanxin, and Wu, Weidong
- Subjects
PARTICULATE matter ,OXIDATIVE stress ,HIGH-fat diet ,FATTY liver ,LIPID metabolism disorders ,DRUG metabolism - Abstract
Background: Chronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM
2.5 ) induces oxidative injury and liver pathogenesis. The present study assessed the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on oxidative stress and hepatic steatosis in the context of a standard chow diet (STD) and a high-fat diet (HFD); the study further explored whether a combination of PM exposure and HFD treatment exacerbates the adverse effects in mice. Methods: C57BL/6J mice fed with STD or HFD (41.26% kcal fat) were exposed to PM or filtered air (FA) for 5 months. Lipid metabolism, oxidative stress and liver pathogenesis were evaluated. Real-time PCR and western blotting were performed to determine gene expression and molecular signal transduction in liver. Results: Chronic airborne PM exposure impaired oxidative homeostasis, caused inflammation and induced hepatic steatosis in mice. Further investigation found that exposure to real-world PM increased the expression of hepatic Nrf2 and Nrf2-regulated antioxidant enzyme gene. The increased protein expression of the sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the liver were also observed in PM-exposed groups. Furthermore, the combination of PM exposure and HFD treatment caused a synergistic effect on the changes of lipid accumulation oxidative stress, inflammation in the mouse liver. Conclusions: Through in vivo study, we reveal that the combination of real-world ambient PM exposure and HFD treatment aggravates hepatic lipid metabolism disorders, inflammation and oxidative stress. PM exposure may accelerate the progression to non-alcoholic steatohepatitis by regulating SREBP-1c/FAS regulatory axis. [ABSTRACT FROM AUTHOR]- Published
- 2019
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