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

» PMID: 38705039 Open Access

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 (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. • Keywords: Apoptosis, Autophagy, Brown adipose tissue, Cellular senescence, Fine particulate matter, Mitochondrial dysfunction • 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