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...
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Language: | English |
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Wiley
2009-01-01
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Series: | PPAR Research |
Online Access: | http://dx.doi.org/10.1155/2009/369602 |
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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 |
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