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Study of Valproic Acid-Enhanced Hepatocyte Steatosis

Authors :
Chih-Hsien Chiu
Mei-Chia Chou
Li-Ying Hung
Renin Chang
Meng-Chieh Hsu
Mu-En Wang
Source :
BioMed Research International, Vol 2016 (2016), BioMed Research International
Publication Year :
2016
Publisher :
Hindawi Limited, 2016.

Abstract

Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-basedin vitromodel. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased, that of carnitine palmitoyltransferase Ia(Cpt1a) was not affected, and those of acetyl-Co A carboxylaseα(Acca) and fatty acid synthase (Fasn) were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptorγ(PPARγ) nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.

Details

ISSN :
23146141 and 23146133
Volume :
2016
Database :
OpenAIRE
Journal :
BioMed Research International
Accession number :
edsair.doi.dedup.....30da25af01a1148c4d87834e79e70c45
Full Text :
https://doi.org/10.1155/2016/9576503