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. Copyright © 2008 by the American Society for Biochemistry and Molecular Biology, Inc.
|Journal||Journal of Lipid Research|
|Publication status||Published - 1 Jan 2008|
- LXR agonist
Calpe-Berdiel, L., Rotllan, N., Fiévet, C., Roig, R., Blanco-Vaca, F., & Escolà-Gil, J. C. (2008). Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8. Journal of Lipid Research, 49(9), 1904-1911. https://doi.org/10.1194/jlr.M700470-JLR200