Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research, Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research, Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Mol Aspects Med. 2018 Dec;64:135-146. doi: 10.1016/j.mam.2018.03.001. Epub 2018 Mar 22.
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.
多年来，人们已经知道高剂量的长链ω-3 脂肪酸对治疗高甘油三酯血症有益。在过去的三十年中，也有大量的体外和体内数据积累，表明长链ω-3 脂肪酸治疗可能有助于降低肝脏三酰甘油。已经确定了几种生物学机制来支持这一假设；值得注意的是，已经表明长链ω-3 脂肪酸具有以下有益作用：a）对涉及炎症途径的生物活性代谢物，b）对核转录因子活性的改变，如过氧化物酶体增殖物激活受体（PPARs）、固醇调节元件结合蛋白 1c（SREBP-1c）和碳水化合物反应元件结合蛋白（ChREBP），这些因子涉及炎症途径和肝脏脂质代谢。由于非酒精性脂肪性肝病（NAFLD）的发病机制始于肝脏脂质的积累，然后发展为炎症，几年后发展为纤维化；因此，人们认为在 NAFLD 患者中，ω-3 脂肪酸治疗将有利于治疗肝脏脂质，并可能改善炎症。荟萃分析（主要是饮食研究和小型试验）倾向于支持ω-3 脂肪酸有益于降低肝脏脂质的说法，但最近的随机对照试验得出了相互矛盾的数据。这些试验表明，ω-3 脂肪酸可能有益于降低肝脏甘油三酯（二十二碳六烯酸可能比二十碳五烯酸更有效），但对改善脂肪性肝炎（或肝纤维化）的其他特征无效。本综述的目的是讨论最近关于长链ω-3 脂肪酸改善 NAFLD 肝脏疾病的生物学机制的证据；考虑最近在成人和儿童 NAFLD 患者中进行的随机试验的证据；最后讨论在计划未来专注于测试ω-3 脂肪酸治疗 NAFLD 患者效果的研究之前，需要考虑的关键“未知的未知”。
