Author, as appears in the article.: Olona, Antoni; Terra, Ximena; Ko, Jeong-Hun; Grau-Bove, Carme; Pinent, Montserrat; Ardevol, Anna; Diaz, Ana Garcia; Moreno-Moral, Aida; Edin, Matthew; Bishop-Bailey, David; Zeldin, Darryl C; Aitman, Timothy J; Petretto, Enrico; Blay, Mayte; Behmoaras, Jacques
Department: Bioquímica i Biotecnologia
URV's Author/s: Ardévol Grau, Anna / Blay Olivé, Maria Teresa / Grau Bové, Maria Carmen / Pinent Armengol, Montserrat / Terra Barbadora, Ximena
Keywords: Steatosis Cytochrome p450 2j4 Cafeteria diet Arachidonic acid Aging Adipogenesis cytochrome p450 2j4 cafeteria diet arachidonic acid aging adipogenesis
Abstract: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions.We took advantage of the simpler genetic architecture of the Cyp2j locus in the rat and used a Cyp2j4 (orthologue of human CYP2J2) knockout rat in two models of metabolic dysfunction: physiological aging and cafeteria diet (CAF). The phenotyping of Cyp2j4-/- rats under CAF was integrated with proteomics (LC-MS/MS) and lipidomics (LC-MS) analyses in the liver and the adipose tissue.We report that Cyp2j4 deletion causes adipocyte dysfunction under metabolic challenges. This is characterized by (i) down-regulation of white adipose tissue (WAT) PPAR? and C/EBP?, (ii) adipocyte hypertrophy, (iii) extracellular matrix remodeling, and (iv) alternative usage of AA pathway. Specifically, in Cyp2j4-/- rats treated with a cafeteria diet, the dysfunctional adipogenesis is accompanied by exacerbated weight gain, hepatic lipid accumulation, and dysregulated gluconeogenesis.These results suggest that AA epoxygenases are essential regulators of healthy adipogenesis. Our results uncover their synergistic role in fine-tuning AA pathway in obesity-mediated hepatic steatosis.Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.
Thematic Areas: Molecular biology Endocrinology & metabolism Ciências biológicas ii Cell biology
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 22128778
Author's mail: mariacarmen.grau@urv.cat mariacarmen.grau@urv.cat mariacarmen.grau@urv.cat anna.ardevol@urv.cat ximena.terra@urv.cat mteresa.blay@urv.cat montserrat.pinent@urv.cat
Author identifier: 0000-0003-0156-7538 0000-0003-1043-5844 0000-0002-6256-9847 0000-0003-3550-5378
Record's date: 2024-10-19
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Molecular Metabolism. 11 18-32
APA: Olona, Antoni; Terra, Ximena; Ko, Jeong-Hun; Grau-Bove, Carme; Pinent, Montserrat; Ardevol, Anna; Diaz, Ana Garcia; Moreno-Moral, Aida; Edin, Matthew; (2018). Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis. Molecular Metabolism, 11(), 18-32. DOI: 10.1016/j.molmet.2018.03.003
Entity: Universitat Rovira i Virgili
Journal publication year: 2018
Publication Type: Journal Publications
Repositori URV