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

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 typ...

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Main Authors: Marite Punapart, Mall Eltermaa, Julia Oflijan, Silva Sütt, Anne Must, Sulev Kõks, Leonard C. Schalkwyk, Catherine Fernandes, Eero Vasar, Ursel Soomets, Anton Terasmaa
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2014/349525
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author Marite Punapart
Mall Eltermaa
Julia Oflijan
Silva Sütt
Anne Must
Sulev Kõks
Leonard C. Schalkwyk
Catherine Fernandes
Eero Vasar
Ursel Soomets
Anton Terasmaa
author_facet Marite Punapart
Mall Eltermaa
Julia Oflijan
Silva Sütt
Anne Must
Sulev Kõks
Leonard C. Schalkwyk
Catherine Fernandes
Eero Vasar
Ursel Soomets
Anton Terasmaa
author_sort Marite Punapart
collection DOAJ
description 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.
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institution Kabale University
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spelling doaj-art-a2cfd09662a04d48ad3bb711a9e2b95e2025-02-03T01:09:44ZengWileyPPAR Research1687-47571687-47652014-01-01201410.1155/2014/349525349525Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout MouseMarite Punapart0Mall Eltermaa1Julia Oflijan2Silva Sütt3Anne Must4Sulev Kõks5Leonard C. Schalkwyk6Catherine Fernandes7Eero Vasar8Ursel Soomets9Anton Terasmaa10Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaSGDP, Institute of Psychiatry at the Maudsley, King’s College London, De Crespigny Park, London SE5 8AF, UKSGDP, Institute of Psychiatry at the Maudsley, King’s College London, De Crespigny Park, London SE5 8AF, UKInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaCentre of Excellence for Translational Medicine, 19 Ravila Street, 50411 Tartu, EstoniaInstitute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, EstoniaValproic 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.http://dx.doi.org/10.1155/2014/349525
spellingShingle Marite Punapart
Mall Eltermaa
Julia Oflijan
Silva Sütt
Anne Must
Sulev Kõks
Leonard C. Schalkwyk
Catherine Fernandes
Eero Vasar
Ursel Soomets
Anton Terasmaa
Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
PPAR Research
title Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
title_full Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
title_fullStr Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
title_full_unstemmed Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
title_short Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile in Wfs1 Knockout Mouse
title_sort effect of chronic valproic acid treatment on hepatic gene expression profile in wfs1 knockout mouse
url http://dx.doi.org/10.1155/2014/349525
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