Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic norma...

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Autores: Dasilva, Gabriel, Lois, Salomé, Méndez, Lucía, Miralles-Pérez, Bernat, Romeu, Marta, Ramos-Romero, Sara, Torres, Josep Lluís, Medina, Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/242258
Acceso en línea:http://hdl.handle.net/10261/242258
Access Level:acceso abierto
Palabra clave:Fish oil
Lipid Mediators
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spelling Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic RatsDasilva, GabrielLois, SaloméMéndez, LucíaMiralles-Pérez, BernatRomeu, MartaRamos-Romero, SaraTorres, Josep LluísMedina, IsabelFish oilLipid MediatorsAdipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.This work was supported by the Spanish Ministry of Science and Innovation (grants AGL2013-49079-C2-1-R and RTI2018-095659-B-I00).Peer reviewedFrontiers MediaMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/242258reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3389/fimmu.2021.608875Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2422582026-05-22T06:33:51Z
dc.title.none.fl_str_mv Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
title Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
spellingShingle Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
Dasilva, Gabriel
Fish oil
Lipid Mediators
title_short Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
title_full Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
title_fullStr Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
title_full_unstemmed Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
title_sort Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats
dc.creator.none.fl_str_mv Dasilva, Gabriel
Lois, Salomé
Méndez, Lucía
Miralles-Pérez, Bernat
Romeu, Marta
Ramos-Romero, Sara
Torres, Josep Lluís
Medina, Isabel
author Dasilva, Gabriel
author_facet Dasilva, Gabriel
Lois, Salomé
Méndez, Lucía
Miralles-Pérez, Bernat
Romeu, Marta
Ramos-Romero, Sara
Torres, Josep Lluís
Medina, Isabel
author_role author
author2 Lois, Salomé
Méndez, Lucía
Miralles-Pérez, Bernat
Romeu, Marta
Ramos-Romero, Sara
Torres, Josep Lluís
Medina, Isabel
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Fish oil
Lipid Mediators
topic Fish oil
Lipid Mediators
description Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/242258
url http://hdl.handle.net/10261/242258
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3389/fimmu.2021.608875
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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