DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model
DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model
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DHA 通过在高脂肪饮食诱导的非酒精性脂肪肝小鼠模型中激活 Sirt1 来预防肝脏脂肪变性
DOI：
10.2147/dmso.s232279
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Luo, Xiaoqin
中科院分区：
文献类型：
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作者：
Luo, Xiao;He, Zhangya;Luo, Xiaoqin
目的二十二碳六烯酸（DHA; C22; n-3）对非酒精性脂肪性肝病（NAFLD）有一定的治疗作用。去乙酰化酶Sirtuin 1（Sirt 1）被报道增加能量代谢和减少脂肪生成。在这里，我们研究了DHA是否通过Sirt 1在预防肝脂肪变性中发挥作用。主要方法采用体内和体外脂肪肝模型：饮食诱导肥胖（diet-induced obesity，DIO）模型（喂饲高脂饮食（high fat diet，HFD）的中年C57 BL/6小鼠）和棕榈酸（palmitic acid，PA）诱导脂质蓄积细胞模型（HepG 2细胞）。在DIO小鼠中，用DHA（灌胃补充剂）治疗8周不仅抑制了脂质积累，还增加了脂肪酸（FA）氧化并诱导肝脏中的甘油三酯输出。这些变化伴随着炎症的减弱。此外，DHA逆转了HFD诱导的肝脏中Sirt 1的减少。有趣的是，慢病毒介导的Sirt 1敲除可以逆转DHA的有益作用，同时脂肪生成、炎症和FA氧化减少标志物的表达增加。在HepG 2细胞中，DHA阻止PA诱导的脂滴积聚，减少FA氧化和降低Sirt 1水平。sirtinol对Sirt 1的抑制部分逆转了DHA对PA处理的细胞的有益作用。DHA通过激活Sirt 1的机制减轻肥胖中年小鼠的肝脏脂肪变性和肝脏炎症。
Aim Docosahexaenoic acid (DHA; C22; n-3) shows beneficial effects on Non-alcoholic fatty liver disease (NAFLD). Deacetylase Sirtuin1 (Sirt1) was reported to increase energy metabolism and decrease lipogenesis. Here, we investigated whether DHA plays a role in protecting against hepatic steatosis via Sirt1. Main Methods Both in vivo and in vitro hepatic steatosis models were used: diet-induced obesity (DIO) model (middle-aged C57BL/6 mice fed a high-fat diet (HFD)) and palmitic acid (PA)-induced lipid accumulation cell model (HepG2 cells). Key Findings In DIO mice, treatment with DHA (gavage supplementation) for 8 weeks not only inhibited the lipid accumulation, but also increased fatty acids (FA) oxidation and induced triglyceride export in liver. These changes were accompanied by attenuation of inflammation. Moreover, DHA reversed the HFD-induced reduction of Sirt1 in liver. Interestingly, the beneficial effects of DHA were reversed by lentivirus-mediated Sirt1 knockdown, accompanied with increased expression of markers of lipogenesis, inflammation and reduced FA oxidation. In HepG2 cells, DHA prevented the accumulation of PA-induced lipid droplets, the decrease of FA oxidation and the reduction of Sirt1 level. Inhibition of Sirt1 by sirtinol partially reversed the beneficial effects of DHA on PA-treated cells. Significance DHA alleviated hepatic steatosis and reduced inflammation of liver in obese middle-aged mice by mechanisms involving Sirt1 activation.