Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
J. Clin. Invest. Mitsuhiro Watanabe, et al. 113:1408 doi:10.1172/JCI21025 [
Go to this article.]
Figure 3Bile acids and SHP decrease expression from the SREBP-1c promoter. (
A) Expression of SREBP-1c and several of its target genes in mouse liver primary hepatocyte cultures. The presence of ligands for LXR (22(R)-hydroxycholesterol, 20 ∝M) and RXR (LG100268, 1 ∝M) is indicated by a + sign. FXR was activated by the addition of CDCA to the medium (50 ∝M and 200 ∝M). (
B) Activity of the mouse SREBP-1c promoter in the McA-RH7777 cell line after the addition of 200 ∝M CDCA or 200 ∝M CA to the medium. Cells were tested in the absence or presence of cotransfected LXRα and ligands for RXR and LXR at the concentrations specified in
A. (
C) Schematic representation of the different constructs of the mouse SREBP-1c promoter used in transfection assays. Binding sites for LXR are displayed as ovals. The nucleotide numbering is relative to the SREBP-1c start codon. (
D) Sequence comparison of the LXRREs in the human and mouse SREBP-1c promoters. The GenBank accession numbers for the human SREBP-1c promoter sequence are NT_010718 or AC122129. (
E) Activity of the mSREBP-1c reporters in McA-RH7777 cells transfected either with an empty expression vector or with the indicated combinations of expression vectors for mouse LRH-1, mouse RXRα, human LXRα, mouse SHP in the presence (black bars) or absence (white bars) of LXR (22(R)-hydroxycholesterol; 20 ∝M) and RXR agonists (LG100268; 1 ∝M).
