Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod
Lipid metabolism is essential in maintaining energy homeostasis in multicellular organisms. In vertebrates, the peroxisome proliferator-activated receptors (PPARs, NR1C) regulate the expression of many genes involved in these processes. Atlantic cod (Gadus morhua) is an important fish species in the North Atlantic ecosystem and in human nutrition, with a highly fatty liver. Here we study the involvement of Atlantic cod Ppar a and b subtypes in systemic regulation of lipid metabolism using two model agonists after in vivo exposure. WY-14,643, a specific PPARA ligand in mammals, activated cod Ppara1 and Ppara2 in vitro. In vivo, WY-14,643 caused a shift in lipid transport both at transcriptional and translational level in cod. However, WY-14,643 induced fewer genes in the fatty acid beta-oxidation pathway compared to that observed in rodents. Although GW501516 serves as a specific PPARB/D ligand in mammals, this compound activated cod Ppara1 and Ppara2 as well as Pparb in vitro. In vivo, it further induced transcription of Ppar target genes and caused changes in lipid composition of liver and plasma. The integrative approach provide a foundation for understanding how Ppars are engaged in regulating lipid metabolism in Atlantic cod physiology. We have shown that WY-14,643 and GW501516 activate Atlantic cod Ppara and Pparb, affect genes in lipid metabolism pathways, and induce changes in the lipid composition in plasma and liver microsomal membranes. Particularly, the combined transcriptomic, proteomics and lipidomics analyses revealed that effects of WY-14,643 on lipid metabolism are similar to what is known in mammalian studies, suggesting conservation of Ppara functions in mediating lipid metabolic processes in fish. The alterations in the lipid profiles observed after Ppar agonist exposure suggest that other chemicals with similar Ppar receptor affinities may cause disturbances in the lipid regulation of fish. Model organism: Atlantic cod (Gadus morhua). LSID: urn:lsid:zoobank.org:act:389BE401-2718-4CF2-BBAE-2E13A97A5E7B. COL Identifier: 6K72F.
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | artículo biblioteca |
Language: | English |
Published: |
Frontiers Media
2023
|
Subjects: | Transcriptomics, GW501516, PPAR, WY-14,643, Fish, Lipidomics, Proteomics, http://metadata.un.org/sdg/6, Ensure availability and sustainable management of water and sanitation for all, |
Online Access: | http://hdl.handle.net/10261/307806 https://api.elsevier.com/content/abstract/scopus_id/85152559867 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
dig-idaea-es-10261-307806 |
---|---|
record_format |
koha |
spelling |
dig-idaea-es-10261-3078062024-05-16T20:39:47Z Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod Eide, Marta Goksøyr, Anders Yadetie, Fekadu Gilabert, Alejandra Bartosova, Zdenka Frøysa, Håvard G. Fallahi, Shirin Zhang, Xiaokang Blaser, Nello Jonassen, Inge Bruheim, Per Alendal, Guttorm Brun, Morten Porte, Cinta Karlsen, Odd André Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all Lipid metabolism is essential in maintaining energy homeostasis in multicellular organisms. In vertebrates, the peroxisome proliferator-activated receptors (PPARs, NR1C) regulate the expression of many genes involved in these processes. Atlantic cod (Gadus morhua) is an important fish species in the North Atlantic ecosystem and in human nutrition, with a highly fatty liver. Here we study the involvement of Atlantic cod Ppar a and b subtypes in systemic regulation of lipid metabolism using two model agonists after in vivo exposure. WY-14,643, a specific PPARA ligand in mammals, activated cod Ppara1 and Ppara2 in vitro. In vivo, WY-14,643 caused a shift in lipid transport both at transcriptional and translational level in cod. However, WY-14,643 induced fewer genes in the fatty acid beta-oxidation pathway compared to that observed in rodents. Although GW501516 serves as a specific PPARB/D ligand in mammals, this compound activated cod Ppara1 and Ppara2 as well as Pparb in vitro. In vivo, it further induced transcription of Ppar target genes and caused changes in lipid composition of liver and plasma. The integrative approach provide a foundation for understanding how Ppars are engaged in regulating lipid metabolism in Atlantic cod physiology. We have shown that WY-14,643 and GW501516 activate Atlantic cod Ppara and Pparb, affect genes in lipid metabolism pathways, and induce changes in the lipid composition in plasma and liver microsomal membranes. Particularly, the combined transcriptomic, proteomics and lipidomics analyses revealed that effects of WY-14,643 on lipid metabolism are similar to what is known in mammalian studies, suggesting conservation of Ppara functions in mediating lipid metabolic processes in fish. The alterations in the lipid profiles observed after Ppar agonist exposure suggest that other chemicals with similar Ppar receptor affinities may cause disturbances in the lipid regulation of fish. Model organism: Atlantic cod (Gadus morhua). LSID: urn:lsid:zoobank.org:act:389BE401-2718-4CF2-BBAE-2E13A97A5E7B. COL Identifier: 6K72F. The study was carried out as part of the project “dCod 1.0: decoding systems toxicology of Atlantic cod” financed by the Norwegian Research Council (project no. 248840) and is part of Centre for Digital Life Norway (DLN), financed by the Research Council of Norway (project no. 248810). This work was also part of the iCod 2.0 project (project no. 244564) financed by the Norwegian Research Council. The UPLC-HRMS analysis was performed in collaboration with another project in DLN, AurOmega (project no. 269432). The Genomics Core Facility (GCF) at the University of Bergen, which is a part of the NorSeq consortium, provided services on RNA sequencing; GCF is supported in part by major grants from the Research Council of Norway (grant no. 245979/F50) and Bergen Research Foundation (BFS) (grant no. BFS2017TMT04 and BFS2017TMT08). Peer reviewed 2023-05-03T05:13:42Z 2023-05-03T05:13:42Z 2023 artículo http://purl.org/coar/resource_type/c_6501 Frontiers in Physiology 14 (2023) 1664-042X http://hdl.handle.net/10261/307806 10.3389/fphys.2023.1129089 37035678 2-s2.0-85152559867 https://api.elsevier.com/content/abstract/scopus_id/85152559867 en Frontiers in physiology Publisher's version https://doi.org/10.3389/fphys.2023.1129089 Sí open Frontiers Media |
institution |
IDAEA ES |
collection |
DSpace |
country |
España |
countrycode |
ES |
component |
Bibliográfico |
access |
En linea |
databasecode |
dig-idaea-es |
tag |
biblioteca |
region |
Europa del Sur |
libraryname |
Biblioteca del IDAEA España |
language |
English |
topic |
Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all |
spellingShingle |
Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all Eide, Marta Goksøyr, Anders Yadetie, Fekadu Gilabert, Alejandra Bartosova, Zdenka Frøysa, Håvard G. Fallahi, Shirin Zhang, Xiaokang Blaser, Nello Jonassen, Inge Bruheim, Per Alendal, Guttorm Brun, Morten Porte, Cinta Karlsen, Odd André Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
description |
Lipid metabolism is essential in maintaining energy homeostasis in multicellular organisms. In vertebrates, the peroxisome proliferator-activated receptors (PPARs, NR1C) regulate the expression of many genes involved in these processes. Atlantic cod (Gadus morhua) is an important fish species in the North Atlantic ecosystem and in human nutrition, with a highly fatty liver. Here we study the involvement of Atlantic cod Ppar a and b subtypes in systemic regulation of lipid metabolism using two model agonists after in vivo exposure. WY-14,643, a specific PPARA ligand in mammals, activated cod Ppara1 and Ppara2 in vitro. In vivo, WY-14,643 caused a shift in lipid transport both at transcriptional and translational level in cod. However, WY-14,643 induced fewer genes in the fatty acid beta-oxidation pathway compared to that observed in rodents. Although GW501516 serves as a specific PPARB/D ligand in mammals, this compound activated cod Ppara1 and Ppara2 as well as Pparb in vitro. In vivo, it further induced transcription of Ppar target genes and caused changes in lipid composition of liver and plasma. The integrative approach provide a foundation for understanding how Ppars are engaged in regulating lipid metabolism in Atlantic cod physiology. We have shown that WY-14,643 and GW501516 activate Atlantic cod Ppara and Pparb, affect genes in lipid metabolism pathways, and induce changes in the lipid composition in plasma and liver microsomal membranes. Particularly, the combined transcriptomic, proteomics and lipidomics analyses revealed that effects of WY-14,643 on lipid metabolism are similar to what is known in mammalian studies, suggesting conservation of Ppara functions in mediating lipid metabolic processes in fish. The alterations in the lipid profiles observed after Ppar agonist exposure suggest that other chemicals with similar Ppar receptor affinities may cause disturbances in the lipid regulation of fish. Model organism: Atlantic cod (Gadus morhua). LSID: urn:lsid:zoobank.org:act:389BE401-2718-4CF2-BBAE-2E13A97A5E7B. COL Identifier: 6K72F. |
format |
artículo |
topic_facet |
Transcriptomics GW501516 PPAR WY-14,643 Fish Lipidomics Proteomics http://metadata.un.org/sdg/6 Ensure availability and sustainable management of water and sanitation for all |
author |
Eide, Marta Goksøyr, Anders Yadetie, Fekadu Gilabert, Alejandra Bartosova, Zdenka Frøysa, Håvard G. Fallahi, Shirin Zhang, Xiaokang Blaser, Nello Jonassen, Inge Bruheim, Per Alendal, Guttorm Brun, Morten Porte, Cinta Karlsen, Odd André |
author_facet |
Eide, Marta Goksøyr, Anders Yadetie, Fekadu Gilabert, Alejandra Bartosova, Zdenka Frøysa, Håvard G. Fallahi, Shirin Zhang, Xiaokang Blaser, Nello Jonassen, Inge Bruheim, Per Alendal, Guttorm Brun, Morten Porte, Cinta Karlsen, Odd André |
author_sort |
Eide, Marta |
title |
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
title_short |
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
title_full |
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
title_fullStr |
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
title_full_unstemmed |
Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod |
title_sort |
integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male atlantic cod |
publisher |
Frontiers Media |
publishDate |
2023 |
url |
http://hdl.handle.net/10261/307806 https://api.elsevier.com/content/abstract/scopus_id/85152559867 |
work_keys_str_mv |
AT eidemarta integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT goksøyranders integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT yadetiefekadu integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT gilabertalejandra integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT bartosovazdenka integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT frøysahavardg integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT fallahishirin integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT zhangxiaokang integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT blasernello integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT jonasseninge integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT bruheimper integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT alendalguttorm integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT brunmorten integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT portecinta integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod AT karlsenoddandre integrativeomicsanalysisoflipidmetabolismregulationbyperoxisomeproliferatoractivatedreceptoraandbagonistsinmaleatlanticcod |
_version_ |
1802820386052636672 |