The expanding role of fish models in understanding non-alcoholic fatty liver disease.
The expanding role of fish models in understanding non-alcoholic fatty liver disease.
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DOI：
10.1242/dmm.011981
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发表时间：
2013-07
影响因子：
4.3
通讯作者：
Nishina H
中科院分区：
文献类型：
--
作者：
Asaoka Y;Terai S;Sakaida I;Nishina H
非酒精性脂肪肝（NAFLD）是一种未过量饮酒的人肝脏中积聚过多脂肪的疾病。非酒精性脂肪性肝炎 (NASH) 是 NAFLD 的一种严重形式，可进展为肝硬化和/或肝细胞癌 (HCC)。 NAFLD 被认为是代谢综合征的肝脏表现，其发病率随着全球肥胖患病率的增加而在全球范围内上升。在过去的十年中，啮齿动物研究已经得出了一系列与 NAFLD 和 NASH 发病机制相关的令人印象深刻的分子。然而，与使用斑马鱼（Danio rerio）和青鳉（Oryzias latipes）等鱼类模型的研究相比，使用哺乳动物模型生物识别当前未知的代谢因子效率低下且昂贵。最近，通过使用小鱼模型进行无偏见的正向遗传筛选，在阐明 NAFLD 的分子发病机制方面取得了实质性进展。此外，这些易于操作的生物体已被用于评估各种化合物治疗 NAFLD 的治疗效果。在这篇综述中，我们总结了先前通过啮齿动物模型揭示的 NAFLD（特别关注 NASH）发病机制的各个方面，并讨论了如何越来越多地使用小鱼来揭示有助于正常肝脏脂质代谢的因素。我们描述了用于此目的的各种类型的鱼类模型，包括通过突变、转基因、饮食或化学处理产生的模型，并将它们与啮齿动物模型进行对比。还讨论了使用小鱼来识别治疗 NAFLD 和 NASH 的新型潜在治疗剂。
Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC). NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH) pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.
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影响因子：
14.8
作者：
通讯作者：
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影响因子：
29.4
作者：
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通讯作者：
Day, CP
影响因子：
11
作者：
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通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
Xie, Wei-Fen
影响因子：
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作者：
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