膜结合型 O-酰基转移酶含域 7 在非酒精性脂肪肝中的关键作用

Livers Pub Date : 2023-12-20 DOI:10.3390/livers4010001
Preethi Chandrasekaran, Ralf Weiskirchen
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引用次数: 0

摘要

非酒精性脂肪肝(NAFLD)是一种常见的流行性疾病,影响着美国 25% 的成年人和全球 32% 的成年人。它是慢性肝病的常见病因之一,以脂肪变性为特征,可导致炎症、纤维化和肝硬化。非酒精性脂肪肝与肥胖和胰岛素抵抗密切相关。目前已持续发现多个基因变异与非酒精性脂肪肝有关,其中一个变异存在于 TMC4-MBOAT7 基因位点。编码溶血磷脂酰肌醇酰基转移酶的 MBOAT7 中的一个变体(rs641738 C>T)会增加非酒精性脂肪肝的发病风险,并通过调节花生四烯酸水平引发肝脏炎症。本综述概述了 MBOAT7 基因、非酒精性脂肪肝的发病机制、对 MBOAT7 调控的理解以及 MBOAT7 与非酒精性脂肪肝之间的机理联系。它进一步总结了与 MBOAT7 相关的体内和体外病理生理学研究,以及治疗复杂的非酒精性脂肪肝所面临的挑战和最近在治疗非酒精性脂肪肝方面取得的进展。因此,本综述提供了有关 MBOAT7 和非酒精性脂肪肝相互关系的有用信息,有可能破译新的治疗靶点,而不是 PNPLA3 和 TM6SF2 等众所周知的基因变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.
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