Multi-omics reveals hypertrophy of adipose tissue and lipid metabolism disorder via mitochondria in young mice under real-ambient exposure to air pollution.

Air pollution has become one of the most serious health risks as a result of industrialization, especially in developing countries. More attention has been drawn to the relationship between obesity/overweight and fine particulate matter (PM2.5). Especially for susceptible populations, the impact of air pollution on children and adolescents has attracted more public attentions. However, the detailed underlying mechanism influencing obesity or overweight under PM2.5 exposure is still unknown. Therefore, young mice were exposed to PM2.5 using the real-ambient exposure system that we previously established in Shijiazhuang city. Compared with the traditionally concentrated air particle (CAP) system, our real-ambient exposure system provides similar PM2.5 concentrations and characteristics as outdoor ambient air and minimizes the influence of external interfering factors. After 8 weeks of exposure to PM2.5, the weight of gonadal white adipose tissue (gWAT) and subcutaneous white adipose tissue (sWAT) was considerably increased, accompanied by a significantly enlarged size of adipocytes in sWAT. Importantly, multiomics analysis indicated altered metabolites involved in the lipid metabolism pathway, and transcriptomic analysis revealed notably changed signaling pathways related to fatty acid metabolism. Moreover, the mtDNA copy number, mitochondrial activity and fatty acid oxidation (FAO) were increased in the liver under PM2.5 exposure. Taken together, our research investigated the hypotrophy of adipose tissue in young mice, supported an imbalance in lipid metabolism based on multiomics analysis, and revealed disordered mitochondrial function under PM2.5 exposure. Our study provided new insight into the hazardous effects of air pollution, and extended our understanding on the underlying mechanism.

The effect of real-ambient PM2.5 exposure on the lung and gut microbiomes and the regulation of Nrf2.

The influence of air pollution on human health has sparked widespread concerns across the world. Previously, we found that exposure to ambient fine particulate matter (PM2.5) in our "real-ambient exposure" system can result in reduced lung function. However, the mechanism of organ-specific toxicity is still not fully elucidated. The balance of the microbiome contributes to maintaining lung and gut health, but the changes in the microbiome under PM2.5 exposure are not fully understood. Recently, crosstalk between nuclear factor E2-related factor 2 (Nrf2) and the microbiome was reported. However, it is unclear whether Nrf2 affects the lung and gut microbiomes under PM2.5 exposure. In this study, wild-type (WT) and Nrf2-/- (KO) mice were exposed to filtered air (FA) and real ambient PM2.5 (PM) in the " real-ambient exposure" system to examine changes in the lung and gut microbiomes. Here, our data suggested microbiome dysbiosis in lung and gut of KO mice under PM2.5 exposure, and Nrf2 ameliorated the microbiome disorder. Our study demonstrated the detrimental impacts of PM2.5 on the lung and gut microbiome by inhaled exposure to air pollution and supported the protective role of Nrf2 in maintaining microbiome homeostasis under PM2.5 exposure.