转酮醇酶调控肝细胞核苷代谢和线粒体功能的机制和应用研究  

Mechanistic and translational study of transketolase-regulated nucleoside metabolism and mitochondrial function in hepatocytes

作　　者：童灵锋 陈章兵 童雪梅 Tong Lingfeng;Chen Zhangbing;Tong Xuemei(Department of Biochemistry and Molecular Cell Biology,Shanghai Jiao Tong Uninversity School of Medicine,Shangha 200025,China)

机构地区：[1]上海交通大学医学院生物化学与分子细胞生物学系,200025

出　　处：《中华内分泌代谢杂志》2025年第1期25-27,共3页Chinese Journal of Endocrinology and Metabolism

摘　　要：本文主要介绍近期发表在《细胞代谢》(Cell Metabolism)的论文《转酮醇酶通过限制次黄嘌呤核苷诱导的线粒体活性促进MAFLD》[Tong L,Chen Z,Li Y,et al.Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity.Cell Metab,2024,36(5):1013-1029.e5]的研究结果,并讨论该研究的科学意义。在代谢异常相关脂肪性肝病(MAFLD)的发生发展中,肝脏时常出现选择性胰岛素抵抗,即肝脏抵抗胰岛素抑制糖异生等作用,但是胰岛素促进肝细胞脂质合成等其他信号通路仍然发挥作用。该研究揭示了转酮醇酶(TKT)在MAFLD发生发展过程中的关键作用。高胰岛素血症选择性促进肝脏TKT转录并导致戊糖代谢紊乱,进而改变核苷代谢稳态,抑制肝细胞线粒体活性和促进MAFLD。此外,该研究证明靶向肝细胞TKT的N-乙酰半乳糖胺偶联小干扰RNA(GalNAc-siTKT)显著改善代谢异常相关脂肪性肝炎(MASH)和肝纤维化。This article reviews a study from Cell Metabolism,titled"Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity"[Tong L,Chen Z,Li Y,et al.Cell Metab.2024,36(5):1013-1029.e5],and discusses its scientific implications.The study explores selective hepatic insulin resistance in metabolic dysfuction-associated fatty liver disease(MAFLD),where insulin stimulates lipid synthesis but not gluconeogenesis in resistant livers.It reveals the key role of transketolase(TKT)in MAFLD progression by disrupting pentose metabolism and nucleoside homeostasis,leading to inhibited mitochondrial activity.Targeting TKT with N-acetylgalactosamine-conjugated small interfering RNA(GalNAc-siTKT)improved metabolic dysfunction-associated steatohepatitis(MASH)and hepatic fibrosis.

关 键 词：转酮醇酶 核苷代谢 线粒体 代谢异常相关脂肪性肝病 

分 类 号：R575.5[医药卫生—消化系统]