Activation of FXR by obeticholic acid induces hepatic gene expression of SR-BI through a novel mechanism of transcriptional synergy with the nuclear receptor LXR.

ABSTRACT: The farnesoid X receptor (FXR) is known to regulate the gene expression of SR‑BI, which mediates plasma high‑density lipoprotein (HDL)‑cholesterol uptake. Our previous study demonstrated that the activation of FXR by obeticholic acid (OCA) lowered plasma HDL‑cholesterol levels and increased the hepatic mRNA and protein expression levels of SR‑BI in hypercholesterolemic hamsters, but not in normolipidemic hamsters, suggesting that dietary cholesterol may be involved in the OCA‑induced transcription of SR‑BI. In the present study, a functional 90‑base‑pair regulatory region was identified in the first intron of the SR‑BI gene of hamster and mouse that contains a FXR response element (IR‑1) and an adjacent liver X receptor (LXR) response element (LXRE). By in vitro DNA binding and luciferase

SUBMITTER: Dong B 

PROVIDER: S-EPMC6443341 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature