Suppression of 2,3-oxidosqualene cyclase by high fat diet contributes to liver X receptor-alpha-mediated improvement of hepatic lipid profile.

ABSTRACT: The liver X receptors (LXRs) sense oxysterols and regulate genes involved in cholesterol metabolism. Synthetic agonists of LXRs are potent stimulators of fatty acid synthesis, which is mediated largely by sterol regulatory element-binding protein-1c (SREBP-1c). Paradoxically, an improved hepatic lipid profile by LXR was observed in mice fed a Western high fat (HF) diet. To explore the underlying mechanism, we administered mice normal chow or an HF diet and overexpressed LXRalpha in the liver. The HF diet with tail-vein injection of adenovirus of LXRalpha increased the expression of LXR-targeted genes involved in cholesterol reverse transport but not those involved in fatty acid synthesis. A similar effect was also observed with the use of 22R-hydroxycholesterol, an LXR ligand, in cultured

SUBMITTER: Dang H 

PROVIDER: S-EPMC2649084 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature