DISTAV, Department of Earth, Environment and Life Sciences, University of Genova, Italy.
Curr Med Chem. 2019;26(19):3439-3456. doi: 10.2174/0929867324666170518101334.
Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity.
Steatosis is a reversible condition that can be resolved with changed behaviors, or that can progress towards more severe liver damages such as steatohepatitis (NASH), fibrosis and cirrhosis. In NAFLD, FA of exogenous or endogenous origin accumulate in the hepatocytes and trigger liver damages. Excess TG are stored in cytosolic lipid droplets (LDs) that are dynamic organelles acting as hubs for lipid metabolism.
In the first part of this review, we briefly reassumed the main classes of FA and their chemical classification as a function of the presence and number of double bonds, their metabolic pathways and effects on human health. Then, we summarized the main genetic and diet-induced animal models of NAFLD, as well as the cellular models of NAFLD.
In recent years, both the diet-induced animal models of NAFLD as well as the cellular models of NAFLD have found ever more application to investigate the mechanisms involved in NAFLD, and we referred to their advantages and disadvantages.
脂肪肝,又称脂肪性肝病,是肝脏内脂质(主要为三酰甘油)过度堆积的一种病症,是一种非酒精性脂肪性肝病(NAFLD)的标志。NAFLD 是全球最常见的肝脏疾病,它经常与肥胖、高血脂和胰岛素抵抗有关。游离脂肪酸(FA)是肝脂肪变性的主要介质;患有 NAFLD 的患者循环 FA 水平升高,与疾病严重程度相关。
脂肪变性是一种可以通过改变行为来逆转的病症,也可以进展为更严重的肝损伤,如脂肪性肝炎(NASH)、纤维化和肝硬化。在 NAFLD 中,外源性或内源性 FA 积聚在肝细胞中并引发肝损伤。过量的三酰甘油储存在胞质脂滴(LDs)中,LDs 是作为脂质代谢枢纽的动态细胞器。
在这篇综述的第一部分,我们简要回顾了 FA 的主要类别及其化学分类,作为存在和双键数量、代谢途径以及对人类健康影响的功能。然后,我们总结了 NAFLD 的主要遗传和饮食诱导的动物模型以及 NAFLD 的细胞模型。
近年来,NAFLD 的饮食诱导动物模型以及 NAFLD 的细胞模型在研究 NAFLD 相关机制方面得到了越来越多的应用,我们参考了它们的优缺点。