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Study of Valproic Acid-Enhanced Hepatocyte Steatosis
- 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.
- Subjects :
- CD36 Antigens
0301 basic medicine
medicine.medical_specialty
Article Subject
Perilipin 2
CD36
lcsh:Medicine
Biology
Perilipin-2
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
Lipid droplet
medicine
Humans
Diacylglycerol O-Acyltransferase
Triglycerides
General Immunology and Microbiology
Valproic Acid
Fatty Acids
lcsh:R
Fatty liver
General Medicine
Lipid Metabolism
medicine.disease
Fatty Liver
Lipoproteins, LDL
PPAR gamma
Fatty acid synthase
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Hepatocyte
Hepatocytes
biology.protein
lipids (amino acids, peptides, and proteins)
Carnitine palmitoyltransferase I
Steatosis
Low Density Lipoprotein Receptor-Related Protein-1
Research Article
Subjects
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