Lingfeng Tong, Zhangbing Chen, Yangyang Li, Xinxia Wang, Changjie Yang, Yakui Li, Yemin Zhu, Ying Lu, Qi Liu, Nannan Xu, Sijia Shao, Lifang Wu, Ping Zhang, Guangyu Wu, Xiaoyu Wu, Xiaosong Chen, Junwei Fang, Renbing Jia, Tianle Xu, Bin Li, Liang Zheng, Junling Liu, Xuemei Tong
Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression...
March 23, 2024: Cell Metabolism