Microsomal prostaglandin E synthase-1 (mPGES-1) is involved in the metabolic and cardiovascular alterations associated with obesity
Entity
UAM. Departamento de FarmacologíaPublisher
Wiley; British Pharmacological SocietyDate
2021-12-07Citation
10.1111/bph.15776
BJP 178.24 (2021): 1-35
ISSN
1476-5381DOI
10.1111/bph.15776Funded by
This work was supported by the Ministerio de Ciencia e Innovación and Fondo Europeo de Desarrollo Regional (FEDER)/FSE (SAF2016-80305P), Instituto de Salud Carlos III (ISCIII; FIS PI18/0257); Comunidad de Madrid (CM) (B2017/BMD-3676 AORTASANA) FEDER-a way to build Europe. MGA was supported by a FPI-UAM fellowship, RRD by a Juan de la Cierva contract (IJCI-2017-31399). The authors thank Victor Gutierrez his help with some experimentsProject
Gobierno de España. SAF2016-80305P; Comunidad de Madrid. B2017/BMD-3676; Gobierno de España. PI18/0257Editor's Version
https://doi.org/10.1111/bph.15776Subjects
mPGES-1; obesity; adipose tissue alterations; vascular function and remodeling; inflammation; Farmacia; MedicinaRights
© 2021 The British Pharmacological SocietyEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional.
Abstract
Microsomal prostaglandin E synthase-1 (mPGES-1) is an
inducible isomerase responsible for prostaglandin E2 production in inflammatory conditions.
We evaluated the role of mPGES-1 in obesity development and in the metabolic and
cardiovascular alterations associated.mPGES-1+/+ and mPGES-1-/- mice were fed with normal or high fat
diet (HFD, 60% fat). The glycaemic and lipid profile was studied by glucose and insulin
tolerance tests and colorimetric assays. Vascular function, structure and mechanics were
evaluated 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 and its correlation with vascular
damage was determined.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 to mPGES-1+/+ mice.
mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial
dysfunction, aortic insulin resistance, and vascular inflammation and remodeling, 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 remodeling, vessel stiffness and systolic
blood pressure. In human PVAT, there was a positive correlation between mPGES-1
expression and inflammatory markers.mPGES-1 inhibition might be a novel therapeutic approach
for the management of obesity and the associated cardiovascular and metabolic alterations
Files in this item
Google Scholar:Ballesteros-Martinez, Constanza
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Rodrigues Díez, Raquel
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Beltrán, Luís M.
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Moreno-Carriles, Rosa
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Martínez-Martínez, Ernesto
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González-Amor, María
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Martínez- González, José
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Rodríguez, Cristina
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Cachofeiro, Victoria
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Salaices Sánchez, Mercedes
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Briones Alonso, Ana María
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