Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity

Background and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E production in inflammatory conditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Appro...

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Autores: Ballesteros-Martínez, Constanza, Rodrigues-Díez, Raquel, Beltrán, Luis M., Moreno-Carriles, Rosa, Martínez-Martínez, Ernesto, González-Amor, María, Martínez-González, José, Rodríguez-Sinovas, Cristina, Cachofeiro, Victoria, Salaices, Mercedes, Briones, Ana M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/288266
Acceso en línea:http://hdl.handle.net/10261/288266
Access Level:acceso abierto
Palabra clave:Adipose tissue alterations
Inflammation
mPGES-1
Obesity
Vascular function and remodelling
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spelling Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesityBallesteros-Martínez, ConstanzaRodrigues-Díez, RaquelBeltrán, Luis M.Moreno-Carriles, RosaMartínez-Martínez, ErnestoGonzález-Amor, MaríaMartínez-González, JoséRodríguez-Sinovas, CristinaCachofeiro, VictoriaSalaices, MercedesBriones, Ana M.Adipose tissue alterationsInflammationmPGES-1ObesityVascular function and remodellingBackground and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E production in inflammatory conditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach: mPGES-1 and mPGES-1 mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glucose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed by myography. Histological studies, q-RT-PCR, and western blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients was correlated with vascular damage. Key Results: Male mPGES-1 mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensitivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared with mPGES-1 mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, induced by HFD. Obesity-induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES-1 mice. In humans, we found a positive correlation between mPGES-1 expression in abdominal fat and vascular remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers. Conclusions and Implications: mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and metabolic alterations.Ministerio Ciencia e Innovación. Programa Juan de la Cierva, Grant/Award Number: IJCI-2017-31399; Comunidad de Madrid, Grant/Award Number: B2017/BMD-3676AORTASANA, FEDER-a way to build Europe;Fondo Europeo de Desarrollo Regional, Grant/Award Number: SAF2016-80305P; Ministeriode Ciencia e Innovacion, Grant/AwardNumber: FIS PI18/0257British Pharmacological SocietyMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Comunidad de MadridEuropean CommissionMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/288266reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//IJCI-2017-31399B2017/BMD-3676/AORTASANAinfo:eu-repo/grantAgreement/MINECO//SAF2016-80305PBallesteros-Martínez, Constanza; Rodrigues-Díez, Raquel; Beltrán, Luis M.; Moreno-Carriles; Moreno-Carriles, Rosa; Martínez-Martínez, Ernesto; González-Amor, María; Martínez-González, José; Rodríguez-Sinovas, Cristina; Cachofeiro, Victoria; Salaices, Mercedes; Briones, Ana M.; 2022; Online supplemental materials Microsomal Prostaglandin E Synthase-1 (mPGES-1) is involved in the metabolic and cardiovascular alterations associated with obesity [Dataset]; British Pharmacological Society; http://dx.doi.org/10.1111/bph.15776http://dx.doi.org/10.1111/bph.15776Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2882662026-05-22T06:33:51Z
dc.title.none.fl_str_mv Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
title Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
spellingShingle Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
Ballesteros-Martínez, Constanza
Adipose tissue alterations
Inflammation
mPGES-1
Obesity
Vascular function and remodelling
title_short Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
title_full Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
title_fullStr Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
title_full_unstemmed Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
title_sort Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
dc.creator.none.fl_str_mv Ballesteros-Martínez, Constanza
Rodrigues-Díez, Raquel
Beltrán, Luis M.
Moreno-Carriles, Rosa
Martínez-Martínez, Ernesto
González-Amor, María
Martínez-González, José
Rodríguez-Sinovas, Cristina
Cachofeiro, Victoria
Salaices, Mercedes
Briones, Ana M.
author Ballesteros-Martínez, Constanza
author_facet Ballesteros-Martínez, Constanza
Rodrigues-Díez, Raquel
Beltrán, Luis M.
Moreno-Carriles, Rosa
Martínez-Martínez, Ernesto
González-Amor, María
Martínez-González, José
Rodríguez-Sinovas, Cristina
Cachofeiro, Victoria
Salaices, Mercedes
Briones, Ana M.
author_role author
author2 Rodrigues-Díez, Raquel
Beltrán, Luis M.
Moreno-Carriles, Rosa
Martínez-Martínez, Ernesto
González-Amor, María
Martínez-González, José
Rodríguez-Sinovas, Cristina
Cachofeiro, Victoria
Salaices, Mercedes
Briones, Ana M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Comunidad de Madrid
European Commission
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Adipose tissue alterations
Inflammation
mPGES-1
Obesity
Vascular function and remodelling
topic Adipose tissue alterations
Inflammation
mPGES-1
Obesity
Vascular function and remodelling
description Background and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E production in inflammatory conditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach: mPGES-1 and mPGES-1 mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glucose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed by myography. Histological studies, q-RT-PCR, and western blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients was correlated with vascular damage. Key Results: Male mPGES-1 mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensitivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared with mPGES-1 mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, induced by HFD. Obesity-induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES-1 mice. In humans, we found a positive correlation between mPGES-1 expression in abdominal fat and vascular remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers. Conclusions and Implications: mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and metabolic alterations.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
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/10261/288266
url http://hdl.handle.net/10261/288266
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//IJCI-2017-31399
B2017/BMD-3676/AORTASANA
info:eu-repo/grantAgreement/MINECO//SAF2016-80305P
Ballesteros-Martínez, Constanza; Rodrigues-Díez, Raquel; Beltrán, Luis M.; Moreno-Carriles; Moreno-Carriles, Rosa; Martínez-Martínez, Ernesto; González-Amor, María; Martínez-González, José; Rodríguez-Sinovas, Cristina; Cachofeiro, Victoria; Salaices, Mercedes; Briones, Ana M.; 2022; Online supplemental materials Microsomal Prostaglandin E Synthase-1 (mPGES-1) is involved in the metabolic and cardiovascular alterations associated with obesity [Dataset]; British Pharmacological Society; http://dx.doi.org/10.1111/bph.15776
http://dx.doi.org/10.1111/bph.15776
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv British Pharmacological Society
publisher.none.fl_str_mv British Pharmacological Society
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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score 15.812455

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