Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs—eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)—in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis.

非酒精性脂肪性肝病（Non-alcoholic fatty liver disease, NAFLD）是代谢综合征的肝脏表现形式，可进展为脂肪性肝炎（steatohepatitis, NASH）及晚期肝损伤，例如肝硬化与肝细胞癌。近期研究证实，摄入n-3多不饱和脂肪酸（n-3 polyunsaturated fatty acids, PUFAs）对非酒精性脂肪性肝病的治疗具有明确益处。本研究旨在探究并比较两种主要n-3多不饱和脂肪酸——二十碳五烯酸（eicosapentaenoic acid, EPA, C20:5）与二十二碳六烯酸（docosahexaenoic acid, DHA, C22:6）——在预防致动脉粥样硬化性高脂（atherogenic high-fat, AHF）饮食诱导的非酒精性脂肪性肝病中的作用效果。实验中，小鼠被喂食添加或不添加EPA或DHA的致动脉粥样硬化性高脂饲料，持续干预4周。结果显示，EPA与DHA均可减轻致动脉粥样硬化性高脂饮食诱导的NASH病理特征，包括肝小叶炎症与血清转氨酶活性升高。值得注意的是，EPA在降低肝脏三酰甘油（triacylglycerol, TG）水平方面的效果优于DHA。与之相反，DHA在抑制致动脉粥样硬化性高脂饮食诱导的肝脏炎症及活性氧（reactive oxygen species, ROS）生成方面的效果更显著，但二者在抗纤维化层面无明显差异。综上，EPA与DHA均可有效用于非酒精性脂肪性肝病及NASH的治疗；同时，这两种主要的n-3多不饱和脂肪酸在介导肝纤维化进展的病理中间环节中的相对贡献或存在差异。