Figure 8.

Fatty acids selectively antagonize transcription-stimulating activity of LXR in HEK-293 cells. Cells were transiently cotransfected with a Gal4-driven luciferase reporter construct; an expression vector containing the Gal4 DNA binding domain fused to the ligand-binding domain of LXRα (A), FXR (B), or RXRα (C) as indicated; and a control plasmid containing the β-galactosidase gene driven by the cytomegalovirus promoter. Six to eight hours after transfection, the natural ligands (5 μM 24(S),25-epoxycholesterol for LXRα, 25 μM chenodeoxycholic acid for FXR, and 50 nM 9-cis retinoic acid for RXRα) and the indicated fatty acids were added to the medium in complex with BSA as described in the legend to Fig. 1. After incubation for 20 h, the cells were harvested for assay. Data are presented as relative luciferase activity normalized to β-galactosidase activity.