Airborne fine particulate matter (PM) 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 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 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 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM 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 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM exposure-induced BAT impairment.

中文翻译：

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PM2.5诱导的细胞衰老导致中年小鼠棕色脂肪组织损伤


空气中细颗粒物（PM）暴露与代谢紊乱密切相关，其中棕色脂肪组织（BAT）是主要贡献器官之一。然而，对 PM 暴露损害 BAT 的表型和机制的了解相当有限。在这项研究中，使用全身吸入暴露系统，将处于三个不同生命阶段（年轻、成年和中年）的雄性 C57BL/6 小鼠同时暴露于浓缩的环境 PM 或过滤空气中 8 周。 H&E 染色和高分辨率呼​​吸测量法用于评估脂肪细胞的大小和线粒体功能。进行转录组学以确定 BAT 中差异表达的基因。通过定量RT-PCR、免疫组化染色和免疫印迹来验证转录组学并探讨BAT线粒体功能障碍的机制。首先，PM 暴露会导致中年小鼠 BAT 形态改变和线粒体功能障碍，但不会影响幼年或成年小鼠。此外，PM 暴露会增加中年小鼠 BAT 中的细胞衰老，并伴有细胞周期停滞、DNA 复制受损并抑制 AKT 信号通路。此外，PM 暴露破坏了中年小鼠 BAT 的细胞凋亡和自噬稳态。因此，中年小鼠的BAT更容易受到PM暴露的影响，细胞衰老引发的凋亡、自噬和线粒体功能障碍可能是PM暴露引起BAT损伤的机制。