《生命科学》 2024, 36(12): 1493-1502

核受体在胎源性非酒精性脂肪肝病中的作用

龚　正^1,2,3 , 戴永国^2,3 , 郭　麒^2,3 , 孙潇翔^2,3 , 郭　喻^1,2,3,*

¹华中科技大学同济医学院附属协和医院药学部，武汉 430022 ²武汉大学基础医学院 药理学系，武汉 430071 ³发育源性疾病湖北省重点实验室，武汉 430071

摘　要：

非酒精性脂肪肝病(nonalcoholic fatty liver disease, NAFLD) 是全球最常见的慢性肝病之一，以肝脏实质细胞脂肪变性为特征，可导致更严重的肝病。越来越多的流行病学和动物研究证明，NAFLD 的发生具有发育起源。在成人NAFLD 的发生发展过程中，核受体作为一种转录因子，在环境或激素信号作用下，调控肝脏脂肪酸代谢相关基因的表达，从而参与或干预NAFLD 的发生。近年来研究显示，生命早期不良环境也会影响核受体的表达和功能，经表观遗传修饰引起其自身或其下游基因表达发生持续性改变，可能参与调控胎源性NAFLD 的发生。本文旨在对核受体在胎源性NAFLD 中的作用及调控机制进行综述。

通讯作者：郭　喻 , Email:guoy@whu.edu.cn

The role of nuclear receptors in fetal-origin non-alcoholic fatty liver disease

GONG Zheng^1,2,3 , DAI Yong-Guo^2,3 , GUO Qi^2,3 , SUN Xiao-Xiang^2,3 , GUO Yu^1,2,3,*

¹Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China ²Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China ³Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China

Abstract:

Non-alcoholic fatty liver disease (NAFLD) is one of the most commonly chronic liver diseases worldwide. It is characterized by hepatic steatosis, which may lead to more severe liver disease. A growing number of epidemiological and animal studies have demonstrated  that NAFLD is a development-originated disease. Nuclear receptors (NRs) are known as transcription factors that  regulate the expression of genes related to metabolism of
fatty acid in the liver, responding to environment or  hormonal signaling. Thereby, NRs participate in or  interfere with the occurrence of NAFLD. Recent studies showed that adverse environment in the early life affects expression and function of the NRs, and epigenetic modifications participate in the continuous alteration of NRs expression or its downstream target genes.  Therefore, NRs may be involved in the occurrence of fetal-origin NAFLD. The role of NRs in fetal-origin NAFLD was reviewed in this manuscript.

Communication Author：GUO Yu , Email:guoy@whu.edu.cn