title: ApoA-I or ABCA1 expression suppresses fatty acid synthesis by reducing 27-hydroxycholesterol levels.
abstract: Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). The ATP-binding cassette transporter A1 (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 1. 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.
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address: yutongw@ccmu.edu.cn.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D002460:Cell Line; D005227:Fatty Acids / Q000096:biosynthesis*; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; C491899:Fas protein, mouse; D005227:Fatty Acids; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D019014:fas Receptor; C076996:27-hydroxycholesterol; D000103:Acetyl-CoA Carboxylase
keywords: ATP-binding cassette transporter; Apolipoprotein A-I; Liver X receptor; Non-alcoholic steatohepatitis