University Hospital Würzburg, Division of Hepatology, Würzburg, Germany.
University of Würzburg, Institute of Pathology, Würzburg, Germany; Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany.
Biochim Biophys Acta Mol Basis Dis. 2019 May 1;1865(5):943-953. doi: 10.1016/j.bbadis.2018.06.023. Epub 2018 Jul 7.
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder closely linked to obesity, hyperlipidemia and type 2 diabetes and is increasingly recognized as a major health problem in many parts of the world. While early stages of NAFLD are characterized by a bland accumulation of fat (steatosis) in hepatocytes, the disease can progress to non-alcoholic steatohepatitis (NASH) which involves chronic liver inflammation, tissue damage and fibrosis and can ultimately lead to end-stage liver disease including cirrhosis and cancer. As no approved pharmacological treatment for NAFLD exists today, there is an urgent need to identify promising pharmacological targets and develop future therapies. For this purpose, basic and translational research in NAFLD animal models is indispensable. While a large number of diverse animal models are currently used in the field, there is an ongoing challenge to identify those models that mirror human pathology the closest to allow good translation of obtained results into further clinical development. This review is meant to provide a concise overview of the most relevant NAFLD animal models currently available and will discuss the strengths and weaknesses of these models with regard to their comparability to human disease conditions.
非酒精性脂肪性肝病(NAFLD)是一种与肥胖、高血脂和 2 型糖尿病密切相关的慢性肝脏疾病,在世界许多地区,它正日益被视为一个主要的健康问题。虽然 NAFLD 的早期阶段以肝细胞内脂肪(脂肪变性)的温和积累为特征,但该疾病可进展为非酒精性脂肪性肝炎(NASH),其涉及慢性肝脏炎症、组织损伤和纤维化,并最终可导致终末期肝病,包括肝硬化和肝癌。由于目前尚无针对 NAFLD 的批准的药物治疗方法,因此迫切需要确定有前途的药物靶点并开发未来的治疗方法。为此,NAFLD 动物模型中的基础和转化研究是必不可少的。虽然目前在该领域使用了大量不同的动物模型,但仍存在一个挑战,即需要确定那些最能模拟人类病理学的模型,以便将获得的结果良好地转化为进一步的临床开发。这篇综述旨在简要概述目前可用的最相关的 NAFLD 动物模型,并将讨论这些模型在与人类疾病状况的可比性方面的优缺点。