Hu 2024 Ecotoxicol Environ Saf
Hu R, Fan W, Li S, Zhang G, Zang L, Qin L, Li R, Chen R, Zhang L, Gu W, Zhang Y, Rajagopalan S, Sun Q, Liu C (2024) PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice. Ecotoxicol Environ Saf 278:116423. https://doi.org/10.1016/j.ecoenv.2024.116423 |
Hu Renjie, Fan Wenjun, Li Sanduo, Zhang Guoqing, Zang Lu, Qin Li, Li Ran, Chen Rucheng, Zhang Lu, Gu Weijia, Zhang Yunhui, Rajagopalan Sanjay, Sun Qinghua, Liu Cuiqing (2024) Ecotoxicol Environ Saf
Abstract: Airborne fine particulate matter (PM2.5) 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 PM2.5 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 PM2.5 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, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment. β’ Keywords: Apoptosis, Autophagy, Brown adipose tissue, Cellular senescence, Fine particulate matter, Mitochondrial dysfunction β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration, Comparative MiP;environmental MiP, Pharmacology;toxicology
Organism: Mouse
Tissue;cell: Fat
Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, CIV, NS, ROX
HRR: Oxygraph-2k
2024-05