Author, as appears in the article.: Olona A, Terra X, Ko JH, Grau-Bové C, Pinent M, Ardevol A, Diaz AG, Moreno-Moral A, Edin M, Bishop-Bailey D, Zeldin DC, Aitman TJ, Petretto E, Blay M, Behmoaras J.

Department: Bioquímica i Biotecnologia

URV's Author/s: Ardèvol Grau, Anna / 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: ximena.terra@urv.cat montserrat.pinent@urv.cat anna.ardevol@urv.cat

Author identifier: 0000-0003-1043-5844 0000-0003-3550-5378 0000-0003-0156-7538

Record's date: 2023-02-26

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S2212877818300711?via%3Dihub

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Molecular Metabolism. 11 18-32

APA: Olona A, Terra X, Ko JH, Grau-Bové C, Pinent M, Ardevol A, Diaz AG, Moreno-Moral A, Edin M, Bishop-Bailey D, Zeldin DC, Aitman TJ, Petretto E, Blay M, (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

Article's DOI: 10.1016/j.molmet.2018.03.003

Entity: Universitat Rovira i Virgili

Journal publication year: 2018

Publication Type: Journal Publications