CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes
Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Un...
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ftntnutrondheimi:oai:ntnuopen.ntnu.no:11250/2600059 2023-05-15T15:30:24+02:00 CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes Winge, Per Datsomor, Alex Olsen, Rolf Erik Jin, Yang Vik, Jon Olav Edvardsen, Rolf Grammes, Fabian Wargelius, Anna Li, Keshuai 2019 http://hdl.handle.net/11250/2600059 https://doi.org/10.1038/s41598-019-43862-8 eng eng Nature Research Scientific Reports. 2019, 9 . urn:issn:2045-2322 http://hdl.handle.net/11250/2600059 https://doi.org/10.1038/s41598-019-43862-8 cristin:1702874 Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no CC-BY 13 9 Scientific Reports Journal article Peer reviewed 2019 ftntnutrondheimi https://doi.org/10.1038/s41598-019-43862-8 2019-09-17T06:55:05Z Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 partial knockout (KO), we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and that endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2-KOs showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-KO salmon showed accumulation of 20:4n-6 in brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of endogenous PUFA synthesis in Atlantic salmon. publishedVersion Open Access. This article is licensed under a Creative Commons Attribution 4.0 International - CC BY 4.0 Article in Journal/Newspaper Atlantic salmon Salmo salar NTNU Open Archive (Norwegian University of Science and Technology) Kos ENVELOPE(143.432,143.432,75.709,75.709) Scientific Reports 9 1 |
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Open Polar |
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NTNU Open Archive (Norwegian University of Science and Technology) |
op_collection_id |
ftntnutrondheimi |
language |
English |
description |
Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 partial knockout (KO), we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and that endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2-KOs showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-KO salmon showed accumulation of 20:4n-6 in brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of endogenous PUFA synthesis in Atlantic salmon. publishedVersion Open Access. This article is licensed under a Creative Commons Attribution 4.0 International - CC BY 4.0 |
format |
Article in Journal/Newspaper |
author |
Winge, Per Datsomor, Alex Olsen, Rolf Erik Jin, Yang Vik, Jon Olav Edvardsen, Rolf Grammes, Fabian Wargelius, Anna Li, Keshuai |
spellingShingle |
Winge, Per Datsomor, Alex Olsen, Rolf Erik Jin, Yang Vik, Jon Olav Edvardsen, Rolf Grammes, Fabian Wargelius, Anna Li, Keshuai CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
author_facet |
Winge, Per Datsomor, Alex Olsen, Rolf Erik Jin, Yang Vik, Jon Olav Edvardsen, Rolf Grammes, Fabian Wargelius, Anna Li, Keshuai |
author_sort |
Winge, Per |
title |
CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
title_short |
CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
title_full |
CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
title_fullStr |
CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
title_full_unstemmed |
CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes |
title_sort |
crispr/cas9-mediated ablation of elovl2 in atlantic salmon (salmo salar l.) inhibits elongation of polyunsaturated fatty acids and induces srebp-1 and target genes |
publisher |
Nature Research |
publishDate |
2019 |
url |
http://hdl.handle.net/11250/2600059 https://doi.org/10.1038/s41598-019-43862-8 |
long_lat |
ENVELOPE(143.432,143.432,75.709,75.709) |
geographic |
Kos |
geographic_facet |
Kos |
genre |
Atlantic salmon Salmo salar |
genre_facet |
Atlantic salmon Salmo salar |
op_source |
13 9 Scientific Reports |
op_relation |
Scientific Reports. 2019, 9 . urn:issn:2045-2322 http://hdl.handle.net/11250/2600059 https://doi.org/10.1038/s41598-019-43862-8 cristin:1702874 |
op_rights |
Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1038/s41598-019-43862-8 |
container_title |
Scientific Reports |
container_volume |
9 |
container_issue |
1 |
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1766360849412259840 |