Targeted metabolomics reveals that 2, 3, 7, 8-tetrachlorodibenzofuran exposure induces hepatic steatosis in male mice. (April 2020)

• Record Type: Journal Article
• Authors: Yuan, Peihong; Dong, Manyuan; Lei, Hehua; Xu, Guangyong; Chen, Gui; Song, Yuchen; Ma, Jianfeng; Cheng, Liming; Zhang, Limin
• Is Part Of: Environmental pollution. Volume 259(2020)
• Publication Date: 2020-04
• Subjects: 2, 3, 7, 8-Tetrachlorodibenzofuran (TCDF) -- Metabolomics -- Hepatic steatosis -- The aryl hydrocarbon receptor; 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.2019.113820
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Environmental exposure to 2, 3, 7, 8-tetrachlorodibenzofuran (TCDF), one of typical persistent organic pollutants (POPs) produced from municipal waste combustion, exerts toxic effects on human healthy. In the current study, we mainly used targeted metabolomics combined with untargeted 1 H NMR-based metabolomics to investigate the effects of TCDF exposure on lipid homeostasis in mice. We found that TCDF exposure induced hepatic lipogenesis, the early-stage of non-alcoholic fatty liver disease, manifested by excessive lipids including triglycerides, fatty acids and lipotoxic ceramides accumulated in the liver together with elevated serum very low-density lipoprotein by activating the aryl hydrocarbon receptor (AHR) and its target genes such as Cyp1a1 and Cd36 . We also found that TCDF exposure induced alteration of phospholipids and choline metabolites and endoplasmic reticulum (ER) markers in the liver of mice, indicating that disruption of host cell membrane structural integrity and ER stress leading to hepatic steatosis. In addition, complementary information was also obtained from histopathologic assessments and biological assays, strongly supporting toxic effects of TCDF. These results provide new evidence of TCDF toxicity associated with fatty liver disease and further our understanding of health effects of environmental pollutants exposure. Graphical abstract: Image 1 Highlights: TCDF induced histopathological fat droplet in mice. TCDF activated AHR and its target genes. TCDF elevated hepatic FAs, TG and Ceramide and serum VLDL.