Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway
Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway
复制标题
维生素 E 通过 Nrf2/CES1 信号通路改善非酒精性脂肪肝小鼠的脂质代谢
DOI：
10.1007/s10620-019-05657-9
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发表时间：
2019-11-01
影响因子：
3.1
通讯作者：
Liu, Dong
中科院分区：
文献类型：
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作者：
He, Wenxi;Xu, Yanjiao;Liu, Dong
研究背景维生素E对非酒精性脂肪性肝病（NAFLD）有一定的治疗作用，但其作用机制尚不明确。Aim：研究维生素E对体内和体外脂肪和葡萄糖稳态的影响。随后，给予NAFLD小鼠维生素E（70 mg/kg）2周。此外，用5 mM果糖和100 nM维生素E处理L02细胞，以探讨潜在的作用机制。结果维生素E逆转果糖处理小鼠的糖耐量受损。组织学检查显示，维生素E治疗的小鼠肝脏脂肪变性明显减轻。这些作用可能归因于核因子红细胞-2相关因子2（Nrf 2），羧酸酯酶1（CES 1）的上调，以及维生素E治疗引起的脂质合成相关蛋白的下调。在体内，维生素E还能显著降低果糖处理的L02细胞的脂质蓄积，而Nrf 2抑制剂ML 385可逆转维生素E的保护作用。结论维生素E对脂糖稳态的治疗作用可能与激活Nrf 2/CES 1信号通路有关。
Background Vitamin E has been reported to have a beneficial effect on nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism of action has not yet been clearly defined.Aim We aimed to evaluate the effects and mechanisms of vitamin E on lipid and glucose homeostasis both in vivo and in vitro.Methods An NAFLD model was established in C57BL/6 mice fed a 30% fructose solution for 8 weeks. Subsequently, NAFLD mice were given vitamin E (70 mg/kg) for 2 weeks. In addition, L02 cells were treated with 5 mM fructose and 100 nM vitamin E to explore the potential mechanisms of action.Results Vitamin E reversed the impaired glucose tolerance of fructose-treated mice. Histopathological examination showed that liver steatosis was significantly relieved in vitamin E-treated mice. These effects may be attributed to the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2), carboxylesterase 1 (CES1), and downregulated proteins involved in lipid synthesis by vitamin E treatment. In vivo, vitamin E also significantly reduced lipid accumulation in fructose-treated L02 cells, and the Nrf2 inhibitor ML385 reversed the protective effects of vitamin E.Conclusion These data indicated that the therapeutic effects of vitamin E on lipid and glucose homeostasis may be associated with activation of the Nrf2/CES1 signaling pathway.