PXR-mediated expression of FABP4 promotes valproate-induced lipid accumulation in HepG2 cells

Abstract

Valproate (valproic acid, VPA) is widely used in the therapy of epilepsy. However, adverse effect like hepatic steatosis has been reported in patients receiving VPA treatment. But whether nuclear receptor pregnane X receptor (PXR) and fatty acid binding protein 4 (FABP4) are involved in the regulation of VPA-induced steatosis or not is still unknown. In this study, the roles of PXR and FABP4 in VPA-induced lipid accumulation in HepG2 cells were investigated. We found that the expression of PXR and FABP4 were increased by VPA in a dose-dependent manner. Knockdown of PXR not only reduced lipid accumulation but also impaired the induction of FABP4 by VPA. While overexpression of PXR enhanced both lipid accumulation and FABP4 expression. Moreover, exogenous expression of FABP4 increased triglyceride levels and enhanced lipid accumulation caused by VPA. Taken together, these results suggest that PXR-mediated expression of FABP4 is responsible for lipid accumulation caused by VPA.