GSE138810
Role of Farnesoid X Receptor (FXR) in Valproic acid-induced Hepatotoxicity
Drug-induced steatosis and steatohepatitis manifest clinically as nonalcoholic fatty liver disease (NAFLD). Drugs associated with steatosis include valproic acid (VPA). VPA has been one of the most widely used antiepileptic drugs over the past 40 years. However, clinical follow-up studies have reported that more than 40% of patients who received VPA also developed fatty liver disease. Steatosis is a typical clinical effect of VPA treatment and is characterized by an abnormal accumulation of lipids in liver cells. The aim of this study is to investigate whether activation of the farnesoid X receptor (FXR) by obeticholic acid (OCA), which is an effective agent in the treatment of NAFLD, can also prevent VPA-induced steatosis. OCA is a synthetic bile acid derivative that potently activates FXR and the FXR-regulated pathways that maintain bile acid, lipid and glucose homeostasis. Female C57BL/6 mice were fed a standard chow diet or chow containing OCA (dose 250 mg/kg body weight) for four weeks. Each group was then divided into two sub-groups: one co-treated with VPA (dose 100 mg/kg body weight) and another treated with the same volume of H2O by oral gavage daily for an additional four weeks. Mice liver were isolated and RNA isolated for RNA-Seq. Overall design: Examination of RNA samples from isolated liver treated either with VPA or VPA+OCA (six female C57BL/6 mice per treatment).