Cross-Omics Analyses Reveal the Effects of Ambient PM_2.5 Exposure on Hepatic Metabolism in Female Mice

Abstract

Ambient particulate matter (PM2.5) is a potential risk factor for metabolic damage to the liver. Epidemiological studies suggest that elevated PM2.5 concentrations cause changes in hepatic metabolism, but there is a lack of laboratory evidence. Here, we aimed to evaluate the effects of PM2.5 exposure on liver metabolism in C57BL/6j female mice (10 months old) and to explore the mechanisms underlying metabolic alterations and differential gene expressions by combining metabolomics and transcriptomics analyses. The metabolomics results showed that PM2.5 exposure notably affected the metabolism of amino acids and organic acids and caused hepatic lipid and bile acid accumulation. The transcriptomic analyses revealed that PM2.5 exposure led to a series of metabolic pathway abnormalities, including steroid biosynthesis, steroid hormone biosynthesis, primary bile acid biosynthesis, etc. Among them, the changes in the bile acid pathway might be one of the causes of liver damage in mice. In conclusion, this study clarified the changes in liver metabolism in mice caused by PM2.5 exposure through combined transcriptomic and metabolomic analyses, revealed that abnormal bile acid metabolism is the key regulatory mechanism leading to metabolic-associated fatty liver disease (MAFLD) in mice, and provided laboratory evidence for further clarifying the effects of PM2.5 on body metabolism.

Keywords

• fine particulate matter
• metabolomics
• transcriptomics
• metabolic-associated fatty liver disease
• bile acids
• lipid