Combined exposure to PM and high-fat diet facilitates the hepatic lipid metabolism disorders via ROS/miR-155/PPARγ pathway.

Environmental fine particulate matter (PM), which has attracted worldwide attention, is associated with the progression of metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether dietary habit exacerbate liver damage caused by PM. The current study aimed to investigate the combined negative effects of PM and high-fat diet (HFD) on liver lipid metabolism in C57BL/6J mice. Histopathological and Oil-Red O staining analysis illustrated that PM exposure resulted in increased liver fat content in HFD-fed C57BL/6J mice, but not in standard chow diet (STD)-fed mice. And there was a synergistic effect between PM and HFD on hepatic lipotoxicity. The increased ROS levels and augmented oxidative damage were evaluated in liver tissue of mice treated with PM and HFD together. In addition, excessive ROS production could activate the miR-155/peroxisome proliferator-activated receptor gamma (PPARγ) pathway, including up-regulation of lipid accumulation-related protein expressions of recombinant liver X receptor alpha (LXRα), sterol regulatory element binding protein-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1).The use of miR-155 inhibitors demonstrated the indispensable role of miR-155 in the activation of lipid-regulated proteins by PM and palmitic acid (PA). Collectively, altering high-fat dietary habits could protect against MAFLD motivated by air pollution, and miR-155 might be an effective preventive and therapeutic target for this process.