Multi-Omics Analysis Reveals Molecular Insights into the Effects of Acute Ozone Exposure on Lung Tissues of Normal and Obese Male Mice

Certain sub-groups, including men and obese individuals, are more susceptible to ozone (O3) exposure, but the underlying molecular mechanisms remain unclear. In this study, the male mice were divided into two dietary groups: one fed a high-fat diet (HFD), mimicking obesity conditions, and the other fed a normal diet (ND), then exposed to 0.5 ppm and 2 ppm O3 for 4 hours per day over two days. The HFD mice exhibited significantly higher body weight and serum lipid biochemical indicators compared to the ND mice. Obese mice also exhibited more severe pulmonary inflammation and oxidative stress. Using a multi-omics approach including proteomics, metabolomics, and lipidomics, we observed that O3 exposure induced significant pulmonary molecular changes in both obese and normal mice, primarily arachidonic acid metabolism and lipid metabolism. Different molecular biomarker responses to acute O3 exposure were also observed between two dietary groups, with immune-related proteins impacted in obese mice and PPAR pathway-related proteins affected in normal mice. Furthermore, although not statistically significant, O3 exposure tended to aggravate HFD-induced disturbances in lung glycerophospholipid metabolism. Overall, this study provides valuable molecular insights into the responses of lung to O3 exposure and highlights the potential impact of O3 on obesity-induced metabolic changes.