Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice

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.