Background: Exposure to persistent organic pollutants (POPs) has been associated with the progression of chronic liver diseases, yet the contribution of POPs to the development of fibrosis in non-alcoholic fatty liver disease (NAFLD), a condition closely linked to obesity, remains poorly documented.
Objectives: We investigated the effects of subchronic exposure to low doses of the POP 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor ligand, on NAFLD progression in diet-induced obese C57BL/6J mice.
Methods: Male C57BL/6J mice were fed either a 10% low-fat (LFD) or a 45% high-fat (HFD) purified diet for 14 weeks and TCDD-exposed groups were injected once a week with 5 μg/kg TCDD or the vehicle for the last 6 weeks of the diet.
Results: Liver histology and triglyceride levels showed that exposure of HFD fed mice to TCDD worsened hepatic steatosis, as compared to either HFD alone or LFD plus TCDD and the mRNA levels of key genes of hepatic lipid metabolism were strongly altered in co-treated mice. Further, increased liver collagen staining and serum transaminase levels showed that TCDD induced liver fibrosis in the HFD fed mice. TCDD in LFD fed mice increased the expression of several inflammation and fibrosis marker genes with no additional effect from a HFD.
Conclusions: Exposure to TCDD amplifies the impairment of liver functions observed in mice fed an enriched fat diet as compared to a low fat diet. The results provide new evidence that environmental pollutants promote the development of liver fibrosis in obesity-related NAFLD in C57BL/6J mice.
1INSERM UMR (Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche)-S1124, Paris, France; 2Université Paris Descartes, ComUE (Communauté d’universités et d’établissements), Sorbonne Paris Cité, Paris, France; 3INSERM UMR-S955, Hôpital Henri Mondor, Créteil, France; 4Université Paris-Est, Créteil, France; 5INSERM UMR-S1166, Paris, France; 6Université Pierre et Marie Curie, Paris, France; 7Department of Environmental and Occupational Health, School of Public Health, Université de Montréal, Montreal, Quebec, Canada; 8AP-HP (Assistance Publique – Hôpitaux de Paris), Hôpital Necker-Enfants Malades, Paris, France
Recommended Citation:
Caroline Duval,1,2 Fatima Teixeira-Clerc,et al. Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in the C57BL/6J Diet-Induced Obesity Mouse Model[J]. Environmental Health Perspectives,2017-01-01,Volume 125(Issue 3):428