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Apolipoprotein A ‐ I and adenosine triphosphate‐binding cassette transporter A 1 expression alleviates lipid accumulation in hepatocytes
Author(s) -
Liu Wei,
Qin Ling,
Yu Hao,
Lv Fangqiao,
Wang Yutong
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12430
Subject(s) - abca1 , apolipoprotein b , endoplasmic reticulum , steatosis , lipoprotein , lipid metabolism , cholesterol , lipid droplet , biochemistry , biology , chemistry , endocrinology , medicine , transporter , gene
Background and Aim Abnormal lipid metabolism may contribute to the pathogenesis of non‐alcoholic steatohepatitis. ATP ‐binding cassette transporter A 1 ( ABCA 1) mediates the transport of cholesterol and phospholipids from cells to high density lipoprotein apolipoproteins. The lipidation of apolipoprotein A ‐ I (apo A ‐ I ) by ABCA 1 is the rate‐limiting step in reverse cholesterol transport and the generation of plasma high density lipoprotein. Here, we examined the effect of apo A ‐ I or ABCA 1 overexpression on hepatic lipid levels in BEL ‐7402 cells. Methods Human ABCA 1 or apo A ‐ I was overexpressed in BEL ‐7402 hepatocytes by transfection and human apo A ‐ I was overexpressed via adenoviral vector in C 57 BL /6 J mice with MCD diet. Results Overexpression of either apo A ‐ I or ABCA 1 resulted in an increase in cholesterol efflux and a decrease in cellular fatty acids and triglycerides. However, after repression of ABCA 1 by its si RNA , overexpression of apo A ‐ I failed to decrease both cellular fatty acids and triglycerides. ApoA ‐ I or ABCA 1 overexpression also resulted in a decrease in the expression of the endoplasmic reticulum stress‐related proteins GRP 78 and SREBP ‐1. Overexpression of apo A ‐ I in mice also reduced hepatic lipid levels. Conclusions Expression of apo A ‐ I or ABCA 1 can reduce steatosis by decreasing lipid storage in hepatocytes through lipid transport and may also reduce endoplasmic reticulum stress, further lessening hepatic steatosis.