脂毒性
脂肪性肝炎
内科学
内分泌学
脂肪肝
天冬氨酸转氨酶
胆固醇
甘油三酯
平衡
丙氨酸转氨酶
化学
下调和上调
生物
医学
生物化学
胰岛素抵抗
基因
碱性磷酸酶
疾病
胰岛素
酶
作者
Yuanhua Dong,Chuwei Yu,Ningning Ma,Xiaoding Xu,Qian Wu,Henglei Lu,Likun Gong,Jing Chen,Jin Ren
标识
DOI:10.1186/s43556-022-00089-w
摘要
Abstract Lipotoxicity induced by the overload of lipid in the liver, especially excess free cholesterol (FC), has been recognized as one of driving factors in the transition from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). MicroRNA (miR)-379-5p has been reported to play regulatory roles in hepatic triglyceride homeostasis, but the relationship of miR-379-5p and hepatic cholesterol homeostasis has never been touched. In the current study, we found that hepatic miR-379-5p levels were decreased obviously in NAFLD patients and model mice compared with their controls. Moreover, miR-379-5p was discovered to be able to inhibit intracellular FC accumulation and alleviate mitochondrial damage induced by palmitic acid (PA) in vitro. Furthermore, overexpression of miR-379-5p in HFHC-fed db/db mice could reduce the level of hepatic total cholesterol (TC) and FC, and ameliorate hepatic injury reflected by the lower serum alanine aminotransferase (ALT) and aspartate transaminase (AST). Subsequently, by combining spectrometry (MS) and luciferase assay, we identified miR-379-5p suppressed STAT1 through transcriptional and translational regulation. Finally, we confirmed that STAT1 was a transcriptional factor of HMGCS1. In conclusion, miR-379-5p inhibits STAT1 expression and regulates cholesterol metabolism through the STAT1/HMGCS1 axis, suggesting miR-379-5p might be applied to improve lipotoxicity in the future.
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