期刊
ENDOCRINE
卷 76, 期 3, 页码 543-557出版社
SPRINGER
DOI: 10.1007/s12020-022-03022-x
关键词
Metformin; PCSK9; HNF-1 alpha; SREBP2; LDL-cholesterol; LDLR
资金
- University of Sharjah, UAE [1701050126P, 1701050126-P, 1901050144]
The intake of Metformin (MF) is associated with reduced levels of LDL-C by suppressing PCSK9 expression and enhancing LDLR expression, indicating its potential therapeutic utility in hypercholesterolemia.
Purpose Metformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous. Methods MF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency. Results MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1 alpha proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity. Conclusions These findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据