Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile.
Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile.
Curr Med Chem. 2020;27(31):5250-5272. doi: 10.2174/0929867326666190410121716.
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.
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.
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.
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.
非酒精性脂肪性肝病（NAFLD）的特征是在没有饮酒的情况下，肝内三酰甘油异常积聚，同时伴有氧化应激（OS）、炎症状态和胰岛素抵抗（IR），这些都可以通过补充 n-3 长链多不饱和脂肪酸（FAs）C20-C22（LCPUFAs）得到缓解。NAFLD 的主要病因包括高热量摄入和久坐的生活方式，以及大量摄入饱和 FAs。
本综述考虑了 n-3 LCPUFAs 在体内和体外 NAFLD 模型中的作用，使用了美国国立卫生研究院-国立医学图书馆的 PubMed 数据库进行了多次搜索。
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）在减轻肝脂肪变性、OS 以及天冬氨酸转氨酶、丙氨酸转氨酶和促炎细胞因子水平方面具有积极作用，同时改善了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描述的 n-3 LCPUFAs 的分子途径包括过氧化物酶体增殖物激活受体-α（PPAR-α）的激活，促进 FA 氧化，固醇反应元件结合蛋白-1c 下调导致脂肪生成减少，以及炎症的解决。此外，n-3 LCPUFA 衍生的氧化产物会激活核因子红细胞 2 相关因子 2（Nrf2），产生直接和间接的抗氧化反应，同时具有抗纤维化作用。
n-3 LCPUFA 补充的讨论效果支持其在 NAFLD 中的应用，尽管在 NASH 中的作用有限，这可能涉及 n-3 LCPUFA 氧化衍生物。未来的研究需要进行临床试验以确定最佳剂量、干预时间、患者类型以及与其他天然产物的可能协同作用。
