Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease.
Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease.
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DOI：
10.1097/cm9.0000000000002092
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发表时间：
2022-05-20
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
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作者：
非酒精性脂肪性肝病（NAFLD）正在成为全球最常见的慢性肝病。它指的是一系列影响很少或不喝酒的人的肝脏疾病。NAFLD包括非酒精性脂肪肝和非酒精性脂肪性肝炎（NASH），这是NAFLD的更具侵袭性的形式。NASH的特征在于脂肪变性、小叶炎症、肝细胞损伤和不同程度的纤维化。虽然在过去的几十年里取得了很大的进展，但NAFLD的致病机制仍有待充分阐明。肝细胞核因子4α（HNF 4 α）是一种在肝细胞中高度表达的核激素受体。在NAFLD患者和NASH小鼠模型中，肝脏HNF 4 α表达显著降低。HNF4α已被证明可调节胆汁酸、脂质、葡萄糖和药物代谢。本文就近年来NAFLD发病机制的研究进展进行综述，重点介绍HNF4α的调控及其在NAFLD中的作用。多项证据表明，肝HNF 4 α在NAFLD的发生和发展中起关键作用。最近的数据表明，肝HNF 4 α可能是治疗NAFLD的一个有希望的靶点。
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.
影响因子：
3.7
作者：
Wirsing A;Senkel S;Klein-Hitpass L;Ryffel GU
通讯作者：
Ryffel GU