内质网（ER）在真核细胞的蛋白质折叠和分泌、Ca2储存和脂质合成中起着关键作用。当需要处理的蛋白质合成和折叠负担超过内质网的处理能力时，错误折叠/未折叠蛋白质的积累会引发内质网应激。为了应对短期内质网应激，未折叠蛋白反应 (UPR) 被激活，使细胞能够生存。当内质网应激严重且持续时，通常会通过多种方法引发细胞死亡。有充分证据表明，内质网应激和代谢失调在功能上是相互交织的，两者都被认为是肝脏疾病发病机制的影响因素，包括非酒精性脂肪性肝病（NAFLD）、酒精性肝病（ALD）、缺血/再灌注（I/ R) 损伤、病毒性肝炎、肝纤维化和肝细胞癌 (HCC)。肝细胞富含光滑内质网和粗糙内质网，其中含有代谢酶，能够感知各种营养状况和外部刺激的变化。广泛的研究集中在内质网应激与代谢酶之间的分子机制上。本综述的目的是总结当前有关 ER 应激对各种肝脏疾病代谢酶影响的知识，并为针对 UPR 的慢性肝病提供潜在的治疗策略。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca2+ storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive. When ER stress is severe and sustained, it typically provokes cell death through multiple approaches. It is well documented that ER stress and metabolic deregulation are functionally intertwined, both are considered contributing factors to the pathogenesis of liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), ischemia/reperfusion (I/R) injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatocytes are rich in smooth and rough ER, which harbor metabolic enzymes that are capable of sensing alterations in various nutritional status and external stimuli. Extensive research has focused on the molecular mechanism linking ER stress with metabolic enzymes. The purpose of this review is to summarize the current knowledge regarding the effects of ER stress on metabolic enzymes in various liver diseases and to provide potential therapeutic strategies for chronic liver diseases via targeting UPR.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.