ApoA-I or ABCA1 expression suppresses fatty acid synthesis by reducing 27-hydroxycholesterol levels

作者：Ma, Donglin; Liu, Wei; Wang, Yutong^*

来源：Biochimie, 2014, 103: 101-108.

DOI：10.1016/j.biochi.2014.04.010

• Apolipoprotein A-I
• ATP-binding cassette transporter
• Non-alcoholic steatohepatitis
• Liver X receptor

Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). The ATP-binding cassette transporter Al (ABCA1) protein mediates the transport of cholesterol and phospholipids from cells to apolipoprotein A-I (apoA-I) to generate nascent HDL particles. Previous studies revealed that overexpression of ABCA1 or apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of apoA-I and ABCA1 overexpression on genes involved in fatty acid synthesis in QSG-7701 hepatocytes and in mice. Human apoA-I and ABCA1 were overexpressed by transfection in QSG-7701 hepatocytes. Human apoA-I was also overexpressed via an adenoviral vector in C57BL/6J mice fed a methionine choline-deficient diet. Overexpression of either apoA-I or ABCA1 resulted in an increase in cholesterol efflux and a decrease in cellular cholesterol, fatty acids, and triglycerides. Overexpression of these genes also resulted in a reduction in 27-hydroxycholesterol levels and a decrease in the mRNA levels of fatty acid synthase and acetyl-CoA carboxylase I. Overexpression of apoA-I in mice reduced hepatic lipid levels, 27-hydroxycholesterol levels, and the mRNA levels of fatty acid synthase and acetyl-CoA carboxylase 1. These results suggest that expression of apoA-I or ABCA1 can reduce steatosis by decreasing lipid storage and modifying lipid transport in hepatocytes and may also inhibit fatty acid synthesis by decreasing 27-hydroxycholesterol levels.

• 出版日期2014-8
• 单位首都医科大学