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Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8

Authors :
Laura Calpe-Berdiel
Noemí Rotllan
Catherine Fiévet
Rosa Roig
Francisco Blanco-Vaca
Joan Carles Escolà-Gil
Source :
Journal of Lipid Research, Vol 49, Iss 9, Pp 1904-1911 (2008)
Publication Year :
2008
Publisher :
Elsevier, 2008.

Abstract

Liver X receptor (LXR) agonists increase both total fecal sterol excretion and macrophage-specific reverse cholesterol transport (RCT) in vivo. In this study, we assessed the effects of ABCG5/G8 deficiency as well as those of LXR agonist-induction of RCT from macrophages to feces in vivo. A [3H]cholesterol-labeled macrophage cell line was injected intraperitoneally into ABCG5/G8-deficient (G5/G8−/−), heterozygous (G5G8+/−), and wild-type G5/G8+/+ mice. G5/G8−/−mice presented increased radiolabeled HDL-bound [3H]cholesterol 24 h after the label injection. However, the magnitude of macrophage-derived [3H]cholesterol in liver and feces did not differ between groups. A separate experiment was conducted in G5G8+/+ and G5G8−/− mice treated with or without the LXR agonist T0901317. Treatment with T0901317 increased liver ABCG5/G8 expression, which was associated with a 2-fold increase in macrophage-derived [3H]cholesterol in feces of G5/G8+/+ mice. However, T0901317 treatment had no effect on fecal [3H]cholesterol excretion in G5G8−/− mice. Additionally, LXR activation stimulated the fecal excretion of labeled cholesterol after an intravenous injection of HDL-[3H]cholesteryl oleate in G5/G8+/+ mice, but failed to enhance fecal [3H]cholesterol in G5/G8−/− mice. Our data provide direct in vivo evidence of the crucial role of ABCG5 and ABCG8 in LXR-mediated induction of macrophage-specific RCT.

Details

Language :
English
ISSN :
00222275
Volume :
49
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Journal of Lipid Research
Publication Type :
Academic Journal
Accession number :
edsdoj.37f1d8ea700409faef95f718f933242
Document Type :
article
Full Text :
https://doi.org/10.1194/jlr.M700470-JLR200