Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα
In humans, in several biological systems, in particular the nervous system, the FADS2 gene transcribes Δ6-desaturase, which is the rate-limiting enzyme for converting α-linolenic acid into docosahexaenoic acid (an n-3 fatty acid). The peroxisome proliferator-activated receptor α (PPARα) modulates th...
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| Format: | Article |
| Language: | English |
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EDP Sciences
2021-01-01
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| Series: | Oilseeds and fats, crops and lipids |
| Subjects: | |
| Online Access: | https://www.ocl-journal.org/articles/ocl/full_html/2021/01/ocl210018/ocl210018.html |
| _version_ | 1818701955447390208 |
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| author | Majou Didier |
| author_facet | Majou Didier |
| author_sort | Majou Didier |
| collection | DOAJ |
| description | In humans, in several biological systems, in particular the nervous system, the FADS2 gene transcribes Δ6-desaturase, which is the rate-limiting enzyme for converting α-linolenic acid into docosahexaenoic acid (an n-3 fatty acid). The peroxisome proliferator-activated receptor α (PPARα) modulates the transcription of FADS2 gene by interacting with a second transcription factor: the retinoid X receptor α (RXRα). These transcription factors take the form of a PPARα-RXRα heterodimer and are modulated by the ligands that modify their respective structures and enable them to bind to the peroxisome proliferator response element (PPRE) located in the promoter region of the FADS2 gene. Free estradiol induces the activation of PPARα via two pathways (i) transcription through genomic action mediated by an estrogen receptor; (ii) a non-genomic effect that allows for phosphorylation and activates PPARα via the ERK1/2-MAPK pathway. Phosphorylation is an on/off switch for PPARα transcription activity. Since Δ6-desaturase expression is retro-inhibited by free intracellular DHA in a dose-dependent manner, this position paper proposes an original hypothesis: if DHA simultaneously binds to both phosphorylated PPARα and RXRα, the resulting DHA-PPARαP-RXRα-DHA heterodimer represses FADS2 gene via PPRE. The retinoic acids-RARα-RXRα-DHA heterodimer would not dissociate from corepressors and would prevent coactivators from binding to FADS2. We speculate that SNPs, which are mostly located on PPRE, modulate the binding affinities of DHA-PPARαP-RXRα-DHA heterodimer to PPRE. The DHA-PPARαP-RXRα-DHA heterodimer’s greater affinity for PPRE results in a decreased production of D6D and DHA. FADS2 promoter polymorphism would increase the competition between DHA and other ligands, in accordance with their concentrations and affinities. |
| first_indexed | 2024-12-17T15:29:04Z |
| format | Article |
| id | doaj.art-da72e7cddd784a8aae03159f0e5afc5e |
| institution | Directory Open Access Journal |
| issn | 2272-6977 2257-6614 |
| language | English |
| last_indexed | 2024-12-17T15:29:04Z |
| publishDate | 2021-01-01 |
| publisher | EDP Sciences |
| record_format | Article |
| series | Oilseeds and fats, crops and lipids |
| spelling | doaj.art-da72e7cddd784a8aae03159f0e5afc5e2022-12-21T21:43:12ZengEDP SciencesOilseeds and fats, crops and lipids2272-69772257-66142021-01-01284310.1051/ocl/2021030ocl210018Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARαMajou DidierIn humans, in several biological systems, in particular the nervous system, the FADS2 gene transcribes Δ6-desaturase, which is the rate-limiting enzyme for converting α-linolenic acid into docosahexaenoic acid (an n-3 fatty acid). The peroxisome proliferator-activated receptor α (PPARα) modulates the transcription of FADS2 gene by interacting with a second transcription factor: the retinoid X receptor α (RXRα). These transcription factors take the form of a PPARα-RXRα heterodimer and are modulated by the ligands that modify their respective structures and enable them to bind to the peroxisome proliferator response element (PPRE) located in the promoter region of the FADS2 gene. Free estradiol induces the activation of PPARα via two pathways (i) transcription through genomic action mediated by an estrogen receptor; (ii) a non-genomic effect that allows for phosphorylation and activates PPARα via the ERK1/2-MAPK pathway. Phosphorylation is an on/off switch for PPARα transcription activity. Since Δ6-desaturase expression is retro-inhibited by free intracellular DHA in a dose-dependent manner, this position paper proposes an original hypothesis: if DHA simultaneously binds to both phosphorylated PPARα and RXRα, the resulting DHA-PPARαP-RXRα-DHA heterodimer represses FADS2 gene via PPRE. The retinoic acids-RARα-RXRα-DHA heterodimer would not dissociate from corepressors and would prevent coactivators from binding to FADS2. We speculate that SNPs, which are mostly located on PPRE, modulate the binding affinities of DHA-PPARαP-RXRα-DHA heterodimer to PPRE. The DHA-PPARαP-RXRα-DHA heterodimer’s greater affinity for PPRE results in a decreased production of D6D and DHA. FADS2 promoter polymorphism would increase the competition between DHA and other ligands, in accordance with their concentrations and affinities.https://www.ocl-journal.org/articles/ocl/full_html/2021/01/ocl210018/ocl210018.htmlfads2δ6-desaturasedhapparαregulation |
| spellingShingle | Majou Didier Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα Oilseeds and fats, crops and lipids fads2 δ6-desaturase dha pparα regulation |
| title | Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα |
| title_full | Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα |
| title_fullStr | Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα |
| title_full_unstemmed | Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα |
| title_short | Synthesis of DHA (omega-3 fatty acid): FADS2 gene polymorphisms and regulation by PPARα |
| title_sort | synthesis of dha omega 3 fatty acid fads2 gene polymorphisms and regulation by pparα |
| topic | fads2 δ6-desaturase dha pparα regulation |
| url | https://www.ocl-journal.org/articles/ocl/full_html/2021/01/ocl210018/ocl210018.html |
| work_keys_str_mv | AT majoudidier synthesisofdhaomega3fattyacidfads2genepolymorphismsandregulationbyppara |