Suppression of ABCA1 by unsaturated fatty acids leads to lipid accumulation in HepG2 cells.
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to HDL apolipoproteins. We previously reported that unsaturated fatty acids destabilise ABCA1 in murine macrophages and ABCA1-transfected baby hamster kidney cells by increasing its protein degradation. Here, we examined the correlation between ABCA1 and hepatic lipids. In HepG2 cells, unsaturated but not saturated fatty acids suppressed ABCA1 protein levels by promoting its protein degradation. Over-expression of ABCA1 resulted in a decrease of cellular fatty acids and triglycerides, while repression by ABCA1 siRNA increased both cellular fatty acids and triglycerides. Rats with NASH also showed lower ABCA1 protein levels in liver cells, compared with that of the normal rats. These data indicate that steatosis is associated with a decrease in ABCA1 protein expression leading to an increase in lipid storage in hepatocytes. And it further suggests that this effect could be due to an excess of unsaturated fatty acids.
Yang
Yanhong
Y
Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China.
Jiang
Ying
Y
Wang
Yutong
Y
An
Wei
W
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D051381:Rats
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D005231:Fatty Acids, Unsaturated