脂肪性肝炎
亚精胺
生物化学
线粒体
生物
细胞生物学
脂肪肝
化学
酶
内科学
医学
疾病
作者
Jin Zhou,Jeremy Pang,Madhulika Tripathi,Jia Pei Ho,Anissa A. Widjaja,Shamini G. Shekeran,Stuart A. Cook,Ayako Suzuki,Anna Mae Diehl,Enrico Petretto,Brijesh K. Singh,Paul M. Yen
标识
DOI:10.1038/s41467-022-32788-x
摘要
Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aH and mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid β-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AH pathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression.
科研通智能强力驱动
Strongly Powered by AbleSci AI