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.


CONCLUSIONS
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.
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guangxi, Guilin 541004, PR China; Faculty of Basic Medicine Science, Guilin Medical University, Guangxi, Guilin 541004, PR China.
Rong
R
Li
Department of Pathology, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China.
Lisheng
L
Liang
Guangxi Medical University, Guangxi, Nanning 530021, PR China.
Xinmou
X
Wu
Department of Pharmacy, Guilin Medical University, Guangxi, Guilin 541004, PR China. Electronic address: college_ma@126.com.
Xianli
X
Ma
Faculty of Basic Medicine Science, Guilin Medical University, Guangxi, Guilin 541004, PR China. Electronic address: college_sumin@126.com.
Min
M
Su
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D000927:Anticonvulsants; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D014635:Valproic Acid
Adipose; FABP4; Metabolism; Vadproate acid