title: Liver-X-receptor-mediated increase in ATP-binding cassette transporter A1 expression is attenuated by fatty acids in CaCo-2 cells: effect on cholesterol efflux to high-density lipoprotein.
abstract: 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.
authors: Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors: Shubha
authors: S
authors: Murthy
authors: Ella
authors: E
authors: Born
authors: Satya N
authors: SN
authors: Mathur
authors: F Jeffrey
authors: FJ
authors: Field
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D001095:Arachidonic Acids / Q000494:pharmacology; D018938:Caco-2 Cells / Q000737:chemistry* / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins; D005227:Fatty Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D000071518:Liver X Receptors; D019301:Oleic Acid / Q000494:pharmacology; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001095:Arachidonic Acids; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019301:Oleic Acid; D002784:Cholesterol