Zheng Wenxiang, Sun Qi, Li Lanlan, Cheng Yi, Chen Yalin, Lv Ming, Xiang Xinxin
Center of Translational Medicine, Zibo Central Hospital, Zibo 255020, Shandong, China.
Weifang Medical University, Weifang 261053, Shandong, China.
Int Immunopharmacol. 2022 Dec;113(Pt B):109458. doi: 10.1016/j.intimp.2022.109458. Epub 2022 Nov 17.
The endoplasmic reticulum is the most abundant membrane organelle in eukaryotic cells. It is an important site of membrane and secretory protein folding and glycolipid synthesis and transport, and it is responsible for regulating intracellular calcium homeostasis. When the load of protein synthesis and folding exceeds the processing capacity of the endoplasmic reticulum, the excessive accumulation of misfolded proteins leads to endoplasmic reticulum stress and activates the cellular unfolded protein response. Hepatocytes contain an abundance of smooth and rough endoplasmic reticulum, which can sense changes in various nutritional metabolic and external stimuli and mediate the regulation of glucose and lipid metabolism by activating the unfolded protein response signaling pathways. Endoplasmic reticulum stress plays a very important role in metabolic regulation and in the occurrence and development of liver diseases. This review summarizes the recent research progress on the unfolded protein response and hepatic glucose and lipid metabolism and discusses the mechanism linking endoplasmic reticulum stress with glucose and lipid metabolism disorders and related metabolic liver diseases to improve the understanding of the molecular pathological basis of major chronic diseases such as obesity, type II diabetes and nonalcoholic fatty liver disease.
内质网是真核细胞中含量最丰富的膜性细胞器。它是膜和分泌蛋白折叠以及糖脂合成与转运的重要场所，负责调节细胞内钙稳态。当蛋白质合成和折叠的负荷超过内质网的加工能力时，错误折叠蛋白的过度积累会导致内质网应激，并激活细胞内未折叠蛋白反应。肝细胞含有丰富的滑面内质网和粗面内质网，它们能够感知各种营养代谢和外部刺激的变化，并通过激活未折叠蛋白反应信号通路介导葡萄糖和脂质代谢的调节。内质网应激在代谢调节以及肝脏疾病的发生和发展中起着非常重要的作用。本文综述了未折叠蛋白反应与肝脏葡萄糖和脂质代谢的最新研究进展，并探讨了内质网应激与葡萄糖和脂质代谢紊乱以及相关代谢性肝病之间的联系机制，以增进对肥胖、II型糖尿病和非酒精性脂肪性肝病等主要慢性疾病分子病理基础的理解。
