PXR 介导的 FABP4 表达促进了丙戊酸诱导的 HepG2 细胞内脂质积累。
PXR-mediated expression of FABP4 promotes valproate-induced lipid accumulation in HepG2 cells.
机构信息
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, 450052, China.
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China.
出版信息
Toxicol Lett. 2021 Aug 1;346:47-56. doi: 10.1016/j.toxlet.2021.04.016. Epub 2021 Apr 24.
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.
丙戊酸（丙戊酸，VPA）广泛用于癫痫的治疗。然而，在接受 VPA 治疗的患者中，已经报道了肝脂肪变性等不良反应。但是，核受体孕烷 X 受体（PXR）和脂肪酸结合蛋白 4（FABP4）是否参与 VPA 诱导的脂肪变性的调节尚不清楚。在这项研究中，研究了 PXR 和 FABP4 在 VPA 诱导的 HepG2 细胞脂质积累中的作用。我们发现，PXR 和 FABP4 的表达随 VPA 剂量呈依赖性增加。PXR 的敲低不仅减少了脂质积累，而且还损害了 VPA 诱导的 FABP4 的诱导。而 PXR 的过表达则增强了脂质积累和 FABP4 的表达。此外，FABP4 的外源性表达增加了三酰甘油水平，并增强了 VPA 引起的脂质积累。总之，这些结果表明，PXR 介导的 FABP4 表达是 VPA 引起的脂质积累的原因。
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