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J Gastroenterol Hepatol. 2014 Mar;29(3):614-22. doi: 10.1111/jgh.12430.

Apolipoprotein A-I and adenosine triphosphate-binding cassette transporter A1 expression alleviates lipid accumulation in hepatocytes.

Author information

1
Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Abstract

BACKGROUND AND AIM:

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.

KEYWORDS:

ATP-binding cassette transporter; apolipoprotein A-I; non-alcoholic steatohepatitis

PMID:
24219083
DOI:
10.1111/jgh.12430
[Indexed for MEDLINE]
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