Effects of differential regional PM induced hepatic steatosis and underlying mechanism.

Emerging evidence suggests that exposure to PM is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM-induced hepatic steatosis remain to be elucidated. In this study, ten-month-old C57BL/6 female mice were exposed to PM from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM exposure. Moreover, Guangzhou PM-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM. This study provides critical information regarding the components of PM, which cause hepatic steatosis.