The effect of fatty acids on LXR (liver X receptors)-mediated enhancement of ABCA1 (ATP-binding cassette transporter A1) expression and cholesterol efflux was investigated in human intestinal cells CaCo-2. LXR activation by T0901317 increased basolateral cholesterol efflux to lipoprotein particles isolated at a density of 1.21 g/ml or higher. Oleic and arachidonic acids attenuated the amount of cholesterol isolated from these particles. Stearic, linoleic and docosahexaenoic acids also decreased cholesterol efflux from basolateral membranes, with the polyunsaturated fatty acids being the most potent. Although oleic, arachidonic and docosahexaenoic acids modestly decreased ABCA1 mRNA levels in response to LXR activation, stearic and linoleic acids did not. Except for oleic acid, all fatty acids substantially attenuated an increase in ABCA1 mass secondary to LXR activation. Inhibiting acyl-CoA:cholesterol acyltransferase activity prevented the decrease in cholesterol efflux caused by oleic acid. Thus, in response to LXR activation, all fatty acids decreased the efflux of cholesterol from the basolateral membrane of CaCo-2 cells. Although modest suppression of ABCA1 gene expression by oleic, arachidonic and docosahexaenoic acids cannot be completely excluded as a mechanism, the predominant effect of fatty acids on ABCA1 expression and cholesterol efflux is at a post-transcriptional level.
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February 01 2004
Liver-X-receptor-mediated increase in ATP-binding cassette transporter A1 expression is attenuated by fatty acids in CaCo- cells: effect on cholesterol efflux to high-density lipoprotein
Shubha MURTHY;
Shubha MURTHY
Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Ella BORN;
Ella BORN
Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Satya N. MATHUR;
Satya N. MATHUR
Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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F. Jeffrey FIELD
F. Jeffrey FIELD
1
Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
June 17 2003
Revision Received:
October 31 2003
Accepted:
November 04 2003
Accepted Manuscript online:
November 04 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 377 (3): 545–552.
Article history
Received:
June 17 2003
Revision Received:
October 31 2003
Accepted:
November 04 2003
Accepted Manuscript online:
November 04 2003
Citation
Shubha MURTHY, Ella BORN, Satya N. MATHUR, F. Jeffrey FIELD; Liver-X-receptor-mediated increase in ATP-binding cassette transporter A1 expression is attenuated by fatty acids in CaCo- cells: effect on cholesterol efflux to high-density lipoprotein. Biochem J 1 February 2004; 377 (3): 545–552. doi: https://doi.org/10.1042/bj20030903
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