糖原发生
脂肪生成
尿苷二磷酸葡萄糖
糖原
化学
甾醇调节元件结合蛋白
内科学
脂质代谢
内分泌学
生物化学
酶
生物
医学
胆固醇
甾醇
糖原合酶
作者
Jie Chen,Yabo Zhou,Zhuohang Liu,Yan Lü,Yuling Jiang,Kexin Cao,Nannan Zhou,Dianheng Wang,Chaoqi Zhang,Ning Zhou,Keqing Shi,Lu Zhang,Li Zhou,Zhenfeng Wang,Huafeng Zhang,Ke Tang,Jingwei Ma,Jiadi Lv,Bo Huang
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-16
卷期号:383 (6684)
被引量:6
标识
DOI:10.1126/science.adi3332
摘要
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.
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