Premium
Down‐regulation of ATP‐binding cassette transporter A1 (ABCA1) and ABCG1 expression by unsaturated fatty acids in vivo and in vitro
Author(s) -
Park YoungKi,
Rasmussen Heather E,
Ehlers Sarah J,
Ku Chai Siah,
Jesch Elliot D,
Carr Timothy P,
Lee JiYoung
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.691.15
Subject(s) - abca1 , abcg1 , agonist , liver x receptor , in vivo , polyunsaturated fatty acid , messenger rna , biology , fatty acid , endocrinology , chemistry , medicine , receptor , biochemistry , transporter , nuclear receptor , gene , microbiology and biotechnology , transcription factor
Regulatory roles of fatty acids (FA) in the expression of ATP binding cassette transporter A1 (ABCA1) and ABCG1 were investigated in vivo and in vitro . Male C57BL/6 mice were fed a modified version of the NIH‐07 diet enriched with palm, sheanut, high oleic acid sunflower or safflower oil (15% fat, 1% Cholesterol by wt) for 4 weeks. The hepatic ABCA1 protein was significantly lowered in the animals fed sheanut, sunflower and safflower oil compared with chow‐fed animals with no changes in mRNA level. HepG2 cells and RAW 264.7 macrophages were incubated with 16:0, 18:0, 18:1, 18:2, 18:3 or EPA (100 μM, 2.5:1 of FA to BSA molar ratio) without or with TO901317 , a liver X receptor (LXR) agonist. In HepG2 cells, ABCA1 mRNA was not altered by FA without TO901317 , but with the agonist, polyunsaturated FA significantly increased ABCA1 mRNA compared with control. In discordance with mRNA, ABCA1 protein was diminished by unsaturated FA both without and with TO901317. In RAW 264.7 macrophages, ABCA1 and ABCG1 mRNA levels were significantly lowered by unsaturated FA without TO901317 whereas the effect of unsaturated FA was abolished in the presence of the agonist. However, unsaturated FA decreased protein levels for ABCA1 and ABCG1 regardless of TO901317. The data suggest that unsaturated FA reduce the expression of ABCA1 and ABCG1 in the liver and macrophages transcriptionally or post‐transcriptionally depending on the site of regulation.