Study of Valproic Acid-Enhanced Hepatocyte Steatosis
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 l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789392/ https://www.ncbi.nlm.nih.gov/pubmed/27034954 http://dx.doi.org/10.1155/2016/9576503 |
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author | Chang, Renin Chou, Mei-Chia Hung, Li-Ying Wang, Mu-En Hsu, Meng-Chieh Chiu, Chih-Hsien |
author_facet | Chang, Renin Chou, Mei-Chia Hung, Li-Ying Wang, Mu-En Hsu, Meng-Chieh Chiu, Chih-Hsien |
author_sort | Chang, Renin |
collection | PubMed |
description | 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-based in vitro model. 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 I a (Cpt1a) was not affected, and those of acetyl-Co A carboxylase α (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 receptor γ (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. |
format | Online Article Text |
id | pubmed-4789392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-47893922016-03-31 Study of Valproic Acid-Enhanced Hepatocyte Steatosis Chang, Renin Chou, Mei-Chia Hung, Li-Ying Wang, Mu-En Hsu, Meng-Chieh Chiu, Chih-Hsien Biomed Res Int Research Article 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-based in vitro model. 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 I a (Cpt1a) was not affected, and those of acetyl-Co A carboxylase α (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 receptor γ (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. Hindawi Publishing Corporation 2016 2016-02-29 /pmc/articles/PMC4789392/ /pubmed/27034954 http://dx.doi.org/10.1155/2016/9576503 Text en Copyright © 2016 Renin Chang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chang, Renin Chou, Mei-Chia Hung, Li-Ying Wang, Mu-En Hsu, Meng-Chieh Chiu, Chih-Hsien Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title | Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title_full | Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title_fullStr | Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title_full_unstemmed | Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title_short | Study of Valproic Acid-Enhanced Hepatocyte Steatosis |
title_sort | study of valproic acid-enhanced hepatocyte steatosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789392/ https://www.ncbi.nlm.nih.gov/pubmed/27034954 http://dx.doi.org/10.1155/2016/9576503 |
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