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Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758)
The elongases of very long-chain fatty acids (Elovls) are responsible for the rate-limiting elongation process in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. The transcription factor, PPARα, regulates lipid metabolism in mammals; however, the detailed mechanism whereby PPARαb regul...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423087/ https://www.ncbi.nlm.nih.gov/pubmed/30886313 http://dx.doi.org/10.1038/s41598-019-41288-w |
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author | Zhu, Ke-Cheng Song, Ling Guo, Hua-Yang Guo, Liang Zhang, Nan Liu, Bao-Suo Jiang, Shi-Gui Zhang, Dian-Chang |
author_facet | Zhu, Ke-Cheng Song, Ling Guo, Hua-Yang Guo, Liang Zhang, Nan Liu, Bao-Suo Jiang, Shi-Gui Zhang, Dian-Chang |
author_sort | Zhu, Ke-Cheng |
collection | PubMed |
description | The elongases of very long-chain fatty acids (Elovls) are responsible for the rate-limiting elongation process in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. The transcription factor, PPARα, regulates lipid metabolism in mammals; however, the detailed mechanism whereby PPARαb regulates Elovls remains largely unknown in fish. In the present study, we report the full length cDNA sequence of Trachinotus ovatus Elovl4a (ToElovl4a), which encodes a 320 amino acid polypeptide that possesses five putative membrane-spanning domains, a conserved HXXHH histidine motif and an ER retrieval signal. Phylogenetic analysis revealed that the deduced protein of ToElovl4a is highly conserved with the Oreochromis niloticus corresponding homologue. Moreover, functional characterization by heterologous expression in yeast indicated that ToElovl4a can elongate C18 up to C20 polyunsaturated fatty acids. A nutritional study showed that the protein expressions of ToElovl4a in the brain and liver were not significantly affected among the different treatments. The region from PGL3-basic-Elovl4a-5 (−148 bp to +258 bp) is defined as the core promoter via a progressive deletion mutation of ToElovl4a. The results from promoter activity assays suggest that ToElovl4a transcription is positively regulated by PPARαb. Mutation analyses indicated that the M2 binding site of PPARαb is functionally important for protein binding, and transcriptional activity of the ToElovl4a promoter significantly decreased after targeted mutation. Furthermore, PPARαb RNA interference reduced ToPPARαb and ToElovl4a expression at the protein levels in a time-dependent manner. In summary, PPARαb may promote the biosynthesis of LC-PUFA by regulating ToElovl4a expression in fish. |
format | Online Article Text |
id | pubmed-6423087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64230872019-03-26 Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) Zhu, Ke-Cheng Song, Ling Guo, Hua-Yang Guo, Liang Zhang, Nan Liu, Bao-Suo Jiang, Shi-Gui Zhang, Dian-Chang Sci Rep Article The elongases of very long-chain fatty acids (Elovls) are responsible for the rate-limiting elongation process in long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. The transcription factor, PPARα, regulates lipid metabolism in mammals; however, the detailed mechanism whereby PPARαb regulates Elovls remains largely unknown in fish. In the present study, we report the full length cDNA sequence of Trachinotus ovatus Elovl4a (ToElovl4a), which encodes a 320 amino acid polypeptide that possesses five putative membrane-spanning domains, a conserved HXXHH histidine motif and an ER retrieval signal. Phylogenetic analysis revealed that the deduced protein of ToElovl4a is highly conserved with the Oreochromis niloticus corresponding homologue. Moreover, functional characterization by heterologous expression in yeast indicated that ToElovl4a can elongate C18 up to C20 polyunsaturated fatty acids. A nutritional study showed that the protein expressions of ToElovl4a in the brain and liver were not significantly affected among the different treatments. The region from PGL3-basic-Elovl4a-5 (−148 bp to +258 bp) is defined as the core promoter via a progressive deletion mutation of ToElovl4a. The results from promoter activity assays suggest that ToElovl4a transcription is positively regulated by PPARαb. Mutation analyses indicated that the M2 binding site of PPARαb is functionally important for protein binding, and transcriptional activity of the ToElovl4a promoter significantly decreased after targeted mutation. Furthermore, PPARαb RNA interference reduced ToPPARαb and ToElovl4a expression at the protein levels in a time-dependent manner. In summary, PPARαb may promote the biosynthesis of LC-PUFA by regulating ToElovl4a expression in fish. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6423087/ /pubmed/30886313 http://dx.doi.org/10.1038/s41598-019-41288-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhu, Ke-Cheng Song, Ling Guo, Hua-Yang Guo, Liang Zhang, Nan Liu, Bao-Suo Jiang, Shi-Gui Zhang, Dian-Chang Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title | Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title_full | Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title_fullStr | Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title_full_unstemmed | Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title_short | Elovl4a participates in LC-PUFA biosynthesis and is regulated by PPARαβ in golden pompano Trachinotus ovatus (Linnaeus 1758) |
title_sort | elovl4a participates in lc-pufa biosynthesis and is regulated by pparαβ in golden pompano trachinotus ovatus (linnaeus 1758) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423087/ https://www.ncbi.nlm.nih.gov/pubmed/30886313 http://dx.doi.org/10.1038/s41598-019-41288-w |
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