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Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8
- 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.
- Subjects :
- HDL
LXR agonist
mice
Biochemistry
QD415-436
Subjects
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