Valproate acid (VPA)-induced dysmetabolic function in clinical and animal studies

Background: Valproate acid (VPA), a commonly used antiepileptic medicine, is found to be linked to developing dysmetabolic risk. However, the proposed mechanism remains completely unknown. Methods: In this study, we collected data from patients with epilepsy and further investigated the preclinical study in mice. Results: As results, the clinical data showed that VPA-used patients resulted in higher levels of blood glucose, urine acid, triglyceride (TG), and immune cells (leucocyte, neutrophil leucocyte) when compared to clinically diagnosed references, while circulating apolipoprotein A1 (Apob A1) and fatty acid binding protein 4 (FABP4) were reduced without visible drug-induced liver injury (DILI). In rodent study, short-term treatment of VPA to mice showed developing trend of metabolic dysfunction, as revealed in increased serum insulin and free fatty acid and TG, and decreased liver TG content. As shown in immunoassay, FABP4 of epididymal white adipose tissue (eWAT) was down-regulated dose-dependently. Conclusion: Collectively, our present findings indicate that VPA can induce FABP4-impaired lipid dysmetabolism without DILI. More notably, FABP4 may function as a sensitive indicator for VPA-induced metabolic dysfunction. (C) 2017 Elsevier B.V. All rights reserved.