机构：[1]Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.[2]Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.[3]Department of Pathology, Sichuan Mianyang 404 Hospital, Sichuan 621000, China.[4]Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.[5]Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China.[6]Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[7]Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.[8]Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
The identification of mechanisms to store glucose carbon in the form of glycogen rather than fat in hepatocytes has important implications for the prevention of nonalcoholic fatty liver disease (NAFLD) and other chronic metabolic diseases. In this work, we show that glycogenesis uses its intermediate metabolite uridine diphosphate glucose (UDPG) to antagonize lipogenesis, thus steering both mouse and human hepatocytes toward storing glucose carbon as glycogen. The underlying mechanism involves transport of UDPG to the Golgi apparatus, where it binds to site-1 protease (S1P) and inhibits S1P-mediated cleavage of sterol regulatory element-binding proteins (SREBPs), thereby inhibiting lipogenesis in hepatocytes. Consistent with this mechanism, UDPG administration is effective at treating NAFLD in a mouse model and human organoids. These findings indicate a potential opportunity to ameliorate disordered fat metabolism in the liver.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.[7]Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
推荐引用方式(GB/T 7714)：
Chen Jie,Zhou Yabo,Liu Zhuohang,et al.Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG[J].Science (New York, N.Y.).2024,383(6684):eadi3332.doi:10.1126/science.adi3332.
APA：
Chen Jie,Zhou Yabo,Liu Zhuohang,Lu Yan,Jiang Yishen...&Huang Bo.(2024).Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG.Science (New York, N.Y.),383,(6684)
MLA：
Chen Jie,et al."Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG".Science (New York, N.Y.) 383..6684(2024):eadi3332
综合性期刊