Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs.

Methods: The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health.

Result: The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator–activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action.

Conclusion: The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.

背景：非酒精性脂肪性肝病（NAFLD）的特征是在没有饮酒的情况下肝甘油三酯的异常蓄积，并伴有氧化应激（OS），促炎状态和胰岛素抵抗（IR），它们均已减弱由n-3个长链多不饱和脂肪酸（FAs）C20-C22（LCPUFAs）补充。NAFLD的主要原因包括高热量摄入和久坐不动的生活方式，以及高摄入饱和脂肪酸。

方法：使用美国国家医学图书馆-美国国立卫生研究院的PubMed数据库，对包括n-3 LCPUFAs在NAFLD体内和体外模型中的影响进行了多次搜索。

结果：LCPUFAs二十碳五烯酸（C20：5 n-3，EPA）和二十二碳六烯酸（C22：6 n-3，DHA）对减少肝脏脂肪变性，OS以及天冬氨酸转氨酶，丙氨酸转氨酶和促炎性细胞因子，改善胰岛素敏感性和脂联素水平。在细胞和动物模型以及人类中，n-3 LCPUFAs的分子途径包括过氧化物酶体增殖物激活的受体-α激活，促进FA氧化，由于固醇响应元件结合蛋白1c下调和脂肪消融而导致的脂肪生成减少。此外，n-3 LCPUFA衍生的氧化产物可引起核因子红系-2-相关因子2活化，产生直接和间接的抗氧化反应，并具有抗纤维化作用。

结论：n-3 LCPUFA补充剂的讨论效应支持其在NAFLD中的使用，尽管在NASH中的价值有限，这一争论可能涉及n-3 LCPUFA氧化衍生物。未来的研究需要确定最佳剂量，干预时间，患者类型以及与其他天然产物可能的协同作用的临床试验。