PM_2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice

Airborne fine particulate matter (PM_2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM_2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM_2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM_2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM_2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM_2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM_2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM_2.5 exposure-induced BAT impairment.