Exposure to 2, 3, 3′, 4, 4′, 5-hexachlorobiphenyl promotes nonalcoholic fatty liver disease development in C57BL/6 mice. (August 2020)

• Record Type: Journal Article
• Authors: Shan, Qiuli; Chen, Ningning; Liu, Wei; Qu, Fan; Chen, Anhui
• Is Part Of: Environmental pollution. Volume 263(2020)Supplement Part A
• Publication Date: 2020-08
• Subjects: NAFLD -- PCB 156 -- Transcriptomics -- Lipid accumulation -- Oxidative stress; NAFLD Non-alcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- PCBs polychlorinated biphenyls -- NHANES National Health and Nutrition Examination Survey -- CD36 CD36 antigen -- Nck2 non-catalytic region of tyrosine kinase adaptor protein 2 -- Gpat2 glycerol-3-phosphate acyltransferase 2 -- Agpat9 1-acylglycerol-3-phosphate O-acyltransferase 9 -- Dgat2 diacylglycerol O-acyltransferase 2 -- Mogat2 monoacylglycerol O-acyltransferase 2 -- Apoc2 apolipoprotein C-II -- Hmgcr 3-hydroxy-3-methylglutaryl-CoA reductase -- Sqle squalene epoxidase -- Lss lanosterol synthase -- Msmol methylsterol monoxygenase 1 -- Cyp7a1 cytochrome P450 family 7 subfamily A member 1 -- Abca1 ATP-binding cassette, sub-family A member 1 -- Srebp1c sterol regulatory element binding transcription factor 1 -- Osbpl3 Oxysterol binding protein-like 3 -- Aacs acetoacetyl-CoA synthetase -- Acsl3 acyl-CoA synthetase long-chain family member 3 -- Cpt1b carnitine palmitoyltransferase 1B -- Ehhadh enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -- Acaa1b acetyl-Coenzyme A acyltransferase 1B -- Cyp1a1 cytochrome P450 family 1 subfamily A member 1 -- Got1 glutamic-oxaloacetic transaminase 1 -- Gstm3 glutathione S-transferase, mu 3 -- Gstm4 glutathione S-transferase, mu 4 -- Nqo1 NAD(P)H dehydrogenase -- CYP450 cytochromeP450 -- AhR aryl hydrocarbon receptor -- ROS reactive oxygen species -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- TC total cholesterol -- TG triglyceride -- HDL-C high-density lipoprotein cholesterol -- LDL-C low-density lipoprotein cholesterol -- MDA malondialdehyde -- SOD superoxide dismutase -- CAT catalase -- GSH-Px glutathione peroxidase; 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.2020.114563
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Previous in vitro studies have indicated that 2, 3, 3′, 4, 4′, 5-hexachlorobiphenyl (PCB 156) may be a new contributor to metabolic disruption and may further cause the occurrence of nonalcoholic fatty liver disease (NAFLD). However, no study has clarified the specific contributions of PCB 156 to NAFLD progression by constructing an in vivo model. Herein, we evaluated the effects of PCB 156 treatment (55 mg/kg, i.p.) on the livers of C57BL/6 mice fed a control diet (CD) or a high-fat diet (HFD). The results showed that PCB 156 administration increased intra-abdominal fat mass, hepatic lipid levels and dyslipidemia in the CD-fed group and aggravated NAFLD in HFD-fed group. By using transcriptomics studies and biological methods, we found that the genes expression involved in lipid metabolism pathways, such as lipogenesis, lipid accumulation and lipid β-oxidation, was greatly altered in liver tissues exposed to PCB 156. In addition, the cytochrome P450 pathway, peroxisome proliferator-activated receptors (PPARs) and the glutathione metabolism pathway were significantly activated following exposure to PCB 156. Furthermore, PCB 156 exposure increased serum transaminase levels and lipid peroxidation, and the redox-related genes were significantly dysregulated in liver tissue. In conclusion, our data suggested that PCB 156 could promote NAFLD development by altering the expression of genes related to lipid metabolism and inducing oxidative stress. Graphical abstract: Image 1 Highlights: In vivo PCB 156 exposure caused hepatic lipid accumulation and dyslipidemia. PCB 156 exposure interfered with the transcriptomics profiles of the liver in mice. Multiple lipid metabolic pathways were disturbed in PCB 156-exposed mice. Oxidative stress played a crucial role in PCB 156-induced fatty liver.