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

Abstract

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.

PM2.5, component cause of severe metabolically abnormal obesity: An in silico, observational and analytical study

“…According to the reports by Rajagopalan et al [ 33 ], it was identified that mice exposed to HFD developed moderately metabolically abnormal obesity, while mice exposed to ∼60–120 μg/m 3 of PM 2.5 exhibited severe abnormal metabolism without obesity. In contrast, Si et al [ 66 ] observed subcutaneous white adipose tissue hypertrophy in mice exposed to PM 2·5 for eight weeks while being fed a normal diet. This discrepancy could be explained based on the origin of the studied white adipose tissue.…”

“…This discrepancy could be explained based on the origin of the studied white adipose tissue. Rajagopalan et al [ 33 ] analyzed adipocytes from epididymal adipose tissue, while Si et al [ 66 ] studied subcutaneous adipose tissue.…”

“…Therefore, the results obtained by Si et al [ 66 ] may be attributed to the high dose of PM 2.5 to which the mice were exposed and the nature of the studied adipose tissue, which has a greater potential for hypertrophy, higher immunological response to foreign agents, and higher weight than visceral adipose tissue. Possibly, the subcutaneous adipose tissue, containing a higher number of immune cells, exhibited an innate response [ 72 ] to the elevated dose of PM 2.5 to which the mice were exposed, in comparison to the exposure dose of the rodents studied by Rajagopalan et al [ 33 ].…”

Environmental PM2.5-triggered stress responses in digestive diseases

“…Mitochondria are exquisitely sensitive to PM 2.5 stimulation in releasing ROS. This has been evidenced in PM 2.5 -exposed macrophages 14 51 and in the lung, 14 52 liver, 14 heart, 53 adipose tissue 54 55 and blood vessels 56 57 of mice or rats exposed to PM 2.5 . With mouse primary hepatic stellate cells and human hepatic stellate cell line LX-2, Qiu et al 22 demonstrated that PM 2.5 exposure triggered the mitophagy process by activating the PINK1/Parkin pathway in a manner depending on mitochondrial ROS release.…”

Emerging technologies in adipose tissue research

“…Multi-omics analyses have helped to understand the clinical relevance of visceral AT in advancing colorectal tumour growth [ 19 ] or the effect of air pollution exposure on obesity [ 20 ]. The datasets created from multi-omics technologies serve as a valuable tool for comparative and translational research on metabolic diseases such as metabolic syndrome and type 2 diabetes mellitus (T2DM).…”