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 E2 production in inflammatory con ditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental App...

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Autores: Ballesteros Martínez, Constanza, Rodrigues Díez, Raquel, Beltrán Romero, Luis Matías, Moreno Carriles, Rosa, Martínez Martínez, Ernesto, González Amor, María, Briones, Ana M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/137971
Acceso en línea:https://hdl.handle.net/11441/137971
https://doi.org/10.1111/bph.15776
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 Romero, Luis MatíasMoreno Carriles, RosaMartínez Martínez, ErnestoGonzález Amor, MaríaBriones, 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 E2 production in inflammatory con ditions. 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 glu cose 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 sensi tivity, 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 meta bolic alterations.Wiley-BlackwellMedicina2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/137971https://doi.org/10.1111/bph.15776reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBRITISH JOURNAL OF PHARMACOLOGY, 179 (11), 2733-2753.https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15776info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1379712026-06-17T12:51:07Z
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 Romero, Luis Matías
Moreno Carriles, Rosa
Martínez Martínez, Ernesto
González Amor, María
Briones, Ana M.
author Ballesteros Martínez, Constanza
author_facet Ballesteros Martínez, Constanza
Rodrigues Díez, Raquel
Beltrán Romero, Luis Matías
Moreno Carriles, Rosa
Martínez Martínez, Ernesto
González Amor, María
Briones, Ana M.
author_role author
author2 Rodrigues Díez, Raquel
Beltrán Romero, Luis Matías
Moreno Carriles, Rosa
Martínez Martínez, Ernesto
González Amor, María
Briones, Ana M.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
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 E2 production in inflammatory con ditions. 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 glu cose 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 sensi tivity, 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 meta bolic alterations.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/137971
https://doi.org/10.1111/bph.15776
url https://hdl.handle.net/11441/137971
https://doi.org/10.1111/bph.15776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BRITISH JOURNAL OF PHARMACOLOGY, 179 (11), 2733-2753.
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15776
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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