6:2 Cl-PFESA has the potential to cause liver damage and induce lipid metabolism disorders in female mice through the action of PPAR-γ. (15th October 2021)

• Record Type: Journal Article
• Authors: Pan, Zihong; Miao, Wenyu; Wang, Caiyun; Tu, Wenqing; Jin, Cuiyuan; Jin, Yuanxiang
• Is Part Of: Environmental pollution. Volume 287(2021)
• Publication Date: 2021-10-15
• Subjects: 6:2 Cl-PFESA -- Metabolism -- Female -- Liver -- PPAR-γ -- 3T3-L1; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.117329
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 6:2 Cl-PFESA is a polyfluoroalkyl ether with high environmental persistence that has been confirmed to have significant adverse effects on animals. In this study, 6-week-old female C57BL/6 mice were exposed to 0, 1, 3 and 10 μg/L 6:2 Cl-PFESA for 10 weeks to estimate the hepatotoxicity of 6:2 Cl-PFESA and explore its underlying molecular mechanism. The results indicated that 6:2 Cl-PFESA preferentially bioaccumulated in the liver and induced hepatic cytoplasmic vacuolation and hepatomegaly in mice. In addition, serum metabolic profiling showed that 6:2 Cl-PFESA exposure caused an abnormal increase in amino acids and an abnormal decrease in acyl-carnitine, which interfered with fatty acid transport and increased the risk of metabolic diseases. Further experiments showed that 6:2 Cl-PFESA formed more hydrogen bonds with PPAR-γ than PFOS, Rosi and GW9662, and the binding affinity of 6:2 Cl-PFESA toward PPAR-γ was the highest among the ligands. 6:2 Cl-PFESA promoted the differentiation of 3T3-L1 cells by increasing PPAR-γ expression. Therefore, our results showed that 6:2 Cl-PFESA has the potential to induce liver damage and dysfunction in female mice, and this effect was achieved through PPAR-γ. This study is the first to reveal the hepatic toxicity of 6:2 Cl-PFESA in female mammals and provides new insights for subsequent in-depth research. Graphical abstract: Image 1 Highlights: 6:2 Cl-PFESA accumulated in the liver and caused liver damage in female mice. 6:2 Cl-PFESA exposure caused induce lipid metabolism disorders by acting on PPAR-γ. 6:2 Cl-PFESA induced differentiation in 3T3-L1 cells. Abstract : In this study, it was confirmed that 6:2 Cl-PFESA could cause liver damage and induce lipid metabolism disorders through the action of PPAR-γ.