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PPAR Research
Volume 2014 (2014), Article ID 349525, 11 pages
http://dx.doi.org/10.1155/2014/349525
Research Article

Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse

1Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia
2Centre of Excellence for Translational Medicine, 19 Ravila Street, 50411 Tartu, Estonia
3SGDP, Institute of Psychiatry at the Maudsley, King’s College London, De Crespigny Park, London SE5 8AF, UK
4Institute of Biomedicine and Translational Medicine, Department of Biochemistry, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia

Received 21 December 2013; Revised 17 February 2014; Accepted 17 February 2014; Published 1 April 2014

Academic Editor: Constantinos Giaginis

Copyright © 2014 Marite Punapart et al. 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.

Abstract

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulate Wfs1 expression in vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) and Wfs1 knockout (KO) mice on hepatic gene expression profile. Wild type, Wfs1 heterozygous, and homozygous mice were treated with VPA for three months (300 mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0 ST array. We identified 42 genes affected by Wfs1 genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not in Wfs1 KO mice. Thus, regulation of Ppard by VPA is dependent on Wfs1 genotype.