Abstract
BackgroundChronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM2.5) 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.MethodsC57BL/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.ResultsChronic 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.ConclusionsThrough 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.
Highlights
Chronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM2.5) induces oxidative injury and liver pathogenesis
We reveal that the combination of real-world ambient PM exposure and high-fat diet (HFD) treatment aggravates hepatic lipid metabolism disorders, inflammation and oxidative stress
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of phenotypes ranging from hepatic steatosis to hepatic nonalcoholic steatohepatitis (NASH), NASH-related fibrosis and cirrhosis [1], which is considered the hepatic manifestation of metabolic syndrome
Summary
C57BL/6J mice fed with STD or HFD (41.26% kcal fat) were exposed to PM or filtered air (FA) for 5 months. Oxidative stress and liver pathogenesis were evaluated. The commercial kits for alanine aminotransferase (ALT), aspartate amino-transferase (AST), malondialdehyde (MDA), oxidized/reduced glutathione (GSSG/GSH), catalase (CAT) and glutathione (GSH) detection were obtained from the Nanjing Jiancheng Bioengineering Institute (Nanjing, China). Serum total triglycerides (TG) and total cholesterol (TC) kits were purchased from BIOSINO Biotechnology and Science, Inc. RNA reverse transcription reagents and the SYBR Premix Ex Taq II kits were obtained from TAKARA Bio, Inc. Rabbit monoclonal F4/80 antibody and rabbit monoclonal anti-LC3B were purchased from Cell Signaling Technology (Billerica, MA, USA). Rabbit monoclonal β-actin antibody, rabbit polyclonal Nrf, Lamin B1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ), SREBP-1c, FAS, acyl CoA oxidase 1 (ACOX1), stearoyl-CoA desaturase 1 (SCD1) antibodies, and the secondary antibody were obtained from Affinity Biosciences, Inc. All chemicals used were of the highest grade commercially available
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