Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in the C57BL/6J Diet-Induced Obesity Mouse Model.
Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in the C57BL/6J Diet-Induced Obesity Mouse Model.
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DOI：
10.1289/ehp316
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发表时间：
2017-03
影响因子：
10.4
通讯作者：
Coumoul X
中科院分区：
文献类型：
--
作者：
Duval C;Teixeira-Clerc F;Leblanc AF;Touch S;Emond C;Guerre-Millo M;Lotersztajn S;Barouki R;Aggerbeck M;Coumoul X
暴露于持久性有机污染物（POP）与慢性肝病的进展有关，但持久性有机污染物对非酒精性脂肪性肝病（NAFLD）纤维化发展的贡献，这是一种与肥胖密切相关的疾病，仍然记录不多。我们研究了亚慢性暴露于低剂量POP 2，3，7，8-四氯二苯并-p-二恶英（TCDD）（一种芳烃受体配体）对饮食诱导的肥胖C57 BL/6 J小鼠NAFLD进展的影响。雄性C57 BL/6 J小鼠连续14周喂食10%低脂（LFD）或45%高脂（HFD）纯化饲料，TCDD暴露组在最后6周每周注射一次5 μg/kg TCDD或溶剂。肝脏组织学和甘油三酯水平显示，与单独的HFD或LFD加TCDD相比，HFD喂养的小鼠暴露于TCDD使肝脏脂肪变性恶化，并且在共同治疗的小鼠中肝脏脂质代谢的关键基因的mRNA水平强烈改变。此外，增加的肝胶原染色和血清转氨酶水平表明，TCDD诱导HFD喂养小鼠的肝纤维化。在LFD喂养的小鼠中，TCDD增加了几种炎症和纤维化标志物基因的表达，而HFD没有额外的影响。与低脂饮食相比，接触TCDD会加剧喂食富脂饮食的小鼠中观察到的肝功能损害。这些结果为环境污染物促进C57 BL/6 J小鼠肥胖相关NAFLD肝纤维化的发展提供了新的证据。Duval C，Teixeira-Clerc F，Leblanc AF，Touch S，Emond C，Guerre-Millo M，Lotersztajn S，Barouki R，Aggerbeck M，Coumoul X. 2017.慢性暴露于低剂量二恶英促进C57 BL/6 J饮食诱导肥胖小鼠模型的肝纤维化发展环境健康展望125：428-436; http：dx.doi.org/10.1289/EHP316
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. 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. 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. 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. 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. Duval C, Teixeira-Clerc F, Leblanc AF, Touch S, Emond C, Guerre-Millo M, Lotersztajn S, Barouki R, Aggerbeck M, Coumoul X. 2017. Chronic exposure to low doses of dioxin promotes liver fibrosis development in the C57BL/6J diet-induced obesity mouse model. Environ Health Perspect 125:428–436; http://dx.doi.org/10.1289/EHP316