出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
