Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment

Omega-3 fatty acids (FAs) have the potential to regulate gene expression via the peroxisome proliferator-activated receptor α (PPARα); therefore, genetic variations in this gene may impact its transcriptional activity on target genes. It is hypothesized that t...

Full description

Saved in:
Bibliographic Details
Main Authors: Iwona Rudkowska, Mélanie Verreault, Olivier Barbier, Marie-Claude Vohl
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2009/369602
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832558765853900800
author Iwona Rudkowska
Mélanie Verreault
Olivier Barbier
Marie-Claude Vohl
author_facet Iwona Rudkowska
Mélanie Verreault
Olivier Barbier
Marie-Claude Vohl
author_sort Iwona Rudkowska
collection DOAJ
description Omega-3 fatty acids (FAs) have the potential to regulate gene expression via the peroxisome proliferator-activated receptor α (PPARα); therefore, genetic variations in this gene may impact its transcriptional activity on target genes. It is hypothesized that the transcriptional activity by wild-type L162-PPARα is enhanced to a greater extent than the mutated variant (V162-PPARα) in the presence of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or a mixture of EPA:DHA. To examine the functional difference of the two allelic variants on receptor activity, transient co-transfections were performed in human hepatoma HepG2 cells activated with EPA, DHA and EPA:DHA mixtures. Results indicate that the addition of EPA or DHA demonstrate potential to increase the transcriptional activity by PPARα with respect to basal level in both variants. Yet, the EPA:DHA mixtures enhanced the transcriptional activity to a greater extent than individual FAs indicating possible additive effects of EPA and DHA. Additionally, the V162 allelic form of PPARα demonstrated consistently lower transcriptional activation when incubated with EPA, DHA or EPA:DHA mixtures than, the wild-type variant. In conclusion, both allelic variants of the PPARα L162V are activated by omega-3 FAs; however, the V162 allelic form displays a lower transcriptional activity than the wild-type variant.
format Article
id doaj-art-f8b8aad2e9a749a69389e8a78d45c892
institution Kabale University
issn 1687-4757
1687-4765
language English
publishDate 2009-01-01
publisher Wiley
record_format Article
series PPAR Research
spelling doaj-art-f8b8aad2e9a749a69389e8a78d45c8922025-02-03T01:31:46ZengWileyPPAR Research1687-47571687-47652009-01-01200910.1155/2009/369602369602Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids TreatmentIwona Rudkowska0Mélanie Verreault1Olivier Barbier2Marie-Claude Vohl3Lipid Research Center, CHUL Research Center, QC, G1V 4G2, CanadaLaboratory of Molecular Pharmacology, Oncology and Genomic Research Center, CHUL Research Center, QC, G1V 4G2, CanadaLaboratory of Molecular Pharmacology, Oncology and Genomic Research Center, CHUL Research Center, QC, G1V 4G2, CanadaLipid Research Center, CHUL Research Center, QC, G1V 4G2, CanadaOmega-3 fatty acids (FAs) have the potential to regulate gene expression via the peroxisome proliferator-activated receptor α (PPARα); therefore, genetic variations in this gene may impact its transcriptional activity on target genes. It is hypothesized that the transcriptional activity by wild-type L162-PPARα is enhanced to a greater extent than the mutated variant (V162-PPARα) in the presence of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or a mixture of EPA:DHA. To examine the functional difference of the two allelic variants on receptor activity, transient co-transfections were performed in human hepatoma HepG2 cells activated with EPA, DHA and EPA:DHA mixtures. Results indicate that the addition of EPA or DHA demonstrate potential to increase the transcriptional activity by PPARα with respect to basal level in both variants. Yet, the EPA:DHA mixtures enhanced the transcriptional activity to a greater extent than individual FAs indicating possible additive effects of EPA and DHA. Additionally, the V162 allelic form of PPARα demonstrated consistently lower transcriptional activation when incubated with EPA, DHA or EPA:DHA mixtures than, the wild-type variant. In conclusion, both allelic variants of the PPARα L162V are activated by omega-3 FAs; however, the V162 allelic form displays a lower transcriptional activity than the wild-type variant.http://dx.doi.org/10.1155/2009/369602
spellingShingle Iwona Rudkowska
Mélanie Verreault
Olivier Barbier
Marie-Claude Vohl
Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
PPAR Research
title Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
title_full Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
title_fullStr Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
title_full_unstemmed Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
title_short Differences in Transcriptional Activation by the Two Allelic (L162V Polymorphic) Variants of PPARα after Omega-3 Fatty Acids Treatment
title_sort differences in transcriptional activation by the two allelic l162v polymorphic variants of pparα after omega 3 fatty acids treatment
url http://dx.doi.org/10.1155/2009/369602
work_keys_str_mv AT iwonarudkowska differencesintranscriptionalactivationbythetwoallelicl162vpolymorphicvariantsofpparaafteromega3fattyacidstreatment
AT melanieverreault differencesintranscriptionalactivationbythetwoallelicl162vpolymorphicvariantsofpparaafteromega3fattyacidstreatment
AT olivierbarbier differencesintranscriptionalactivationbythetwoallelicl162vpolymorphicvariantsofpparaafteromega3fattyacidstreatment
AT marieclaudevohl differencesintranscriptionalactivationbythetwoallelicl162vpolymorphicvariantsofpparaafteromega3fattyacidstreatment