Autor según el artículo: 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.

Departamento: Bioquímica i Biotecnologia

Autor/es de la URV: Ardèvol Grau, Anna / Pinent Armengol, Montserrat / Terra Barbadora, Ximena

Palabras clave: Steatosis Cytochrome p450 2j4 Cafeteria diet Arachidonic acid Aging Adipogenesis cytochrome p450 2j4 cafeteria diet arachidonic acid aging adipogenesis

Resumen: 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.

Áreas temáticas: Molecular biology Endocrinology & metabolism Ciências biológicas ii Cell biology

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 22128778

Direcció de correo del autor: ximena.terra@urv.cat montserrat.pinent@urv.cat anna.ardevol@urv.cat

Identificador del autor: 0000-0003-1043-5844 0000-0003-3550-5378 0000-0003-0156-7538

Fecha de alta del registro: 2023-02-26

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.sciencedirect.com/science/article/pii/S2212877818300711?via%3Dihub

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Molecular Metabolism. 11 18-32

Referencia de l'ítem segons les normes 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

DOI del artículo: 10.1016/j.molmet.2018.03.003

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2018

Tipo de publicación: Journal Publications