The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2.

ABSTRACT:

Objective

To determine whether activation of farnesoid X receptor (FXR) alters cellular and plasma cholesterol homeostasis as a result of regulation of Srebp-2 and miR-33.

Approach and results

Chromatin immunoprecipitation sequencing data identified an FXR response element within intron 10 of the Srebp-2 gene. Consistent with this observation, treatment of mice with FXR-specific agonists (GSK2324 or GW4064) rapidly increased hepatic levels of Srebp-2 mRNA, precursor sterol response element binding protein 2 (pSREBP-2) protein, and miR-33. Furthermore, miR-33 targets, that include ABCA1 (ATP binding cassette transporter A1), NSF (N-ethylmaleimide-sensitive factor), and CPT1 (carnitine palmitoyltransferase 1), were all reduced in GSK2324-treated mice. In contrast, neither nucl

SUBMITTER: Tarling EJ 

PROVIDER: S-EPMC4376635 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature