Apolipoprotein A-I and adenosine triphosphate-binding cassette transporter A1 expression alleviates lipid accumulation in hepatocytes.
OBJECTIVE
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to high density lipoprotein apolipoproteins. The lipidation of apolipoprotein A-I (apoA-I) by ABCA1 is the rate-limiting step in reverse cholesterol transport and the generation of plasma high density lipoprotein. Here, we examined the effect of apoA-I or ABCA1 overexpression on hepatic lipid levels in BEL-7402 cells.


METHODS
Human ABCA1 or apoA-I was overexpressed in BEL-7402 hepatocytes by transfection and human apoA-I was overexpressed via adenoviral vector in C57BL/6J mice with MCD diet.


RESULTS
Overexpression of either apoA-I or ABCA1 resulted in an increase in cholesterol efflux and a decrease in cellular fatty acids and triglycerides. However, after repression of ABCA1 by its siRNA, overexpression of apoA-I failed to decrease both cellular fatty acids and triglycerides. ApoA-I or ABCA1 overexpression also resulted in a decrease in the expression of the endoplasmic reticulum stress-related proteins GRP78 and SREBP-1. Overexpression of apoA-I in mice also reduced hepatic lipid levels.


CONCLUSIONS
Expression of apoA-I or ABCA1 can reduce steatosis by decreasing lipid storage in hepatocytes through lipid transport and may also reduce endoplasmic reticulum stress, further lessening hepatic steatosis.
Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Wei
W
Liu
Ling
L
Qin
Hao
H
Yu
Fangqiao
F
Lv
Yutong
Y
Wang
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1
ATP-binding cassette transporter; apolipoprotein A-I; non-alcoholic steatohepatitis