Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue.

Caloric restriction Exercise Human obesity Metabolic fingerprint Metabolic plasticity Mitochondrial dysfunction Multi-organ approach Obesity Two-steps bariatric surgery Visceral adipose tissue

Journal

Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639

Informations de publication

Date de publication:
08 2022
Historique:
received: 16 03 2022
revised: 20 05 2022
accepted: 24 05 2022
pubmed: 2 7 2022
medline: 14 7 2022
entrez: 1 7 2022
Statut: ppublish

Résumé

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.

Identifiants

pubmed: 35777200
pii: S2213-2317(22)00125-2
doi: 10.1016/j.redox.2022.102353
pmc: PMC9287736
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

102353

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

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Auteurs

Alba Gonzalez-Franquesa (A)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.

Pau Gama-Perez (P)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain.

Marta Kulis (M)

Biomedical Epigenomics Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Karolina Szczepanowska (K)

Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), and Institute for Mitochondrial Diseases and Ageing, Medical Faculty, University of Cologne, D-50931, Cologne, Germany.

Norma Dahdah (N)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain.

Sonia Moreno-Gomez (S)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain.

Ana Latorre-Pellicer (A)

Grupo de Medicina Xenómica, CIBERER, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, 50009, Zaragoza, Spain.

Rebeca Fernández-Ruiz (R)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain; Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain.

Antoni Aguilar-Mogas (A)

Department of Chemical Engineering, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

Anne Hoffman (A)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.

Erika Monelli (E)

Vascular Signalling Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907, Barcelona, Spain.

Sara Samino (S)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Department of Electronic Engineering, IISPV, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

Joan Miró-Blanch (J)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Department of Electronic Engineering, IISPV, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

Gregor Oemer (G)

Institute of Human Genetics, Medical University of Innsbruck, 6020, Innsbruck, Austria.

Xavier Duran (X)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Institut d'Investigació Sanitària Pere Virgili, Endocrinology and Nutrition Service, Hospital Universitari de Tarragona Joan XXIII, 43007, Tarragona, Spain.

Estrella Sanchez-Rebordelo (E)

Department of Physiology, CIMUS, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain.

Marc Schneeberger (M)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, NY, 10065, New York, USA.

Merce Obach (M)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Joel Montane (J)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; Blanquerna School of Health Science, Ramon Llull University, Barcelona, Spain.

Giancarlo Castellano (G)

Biomedical Epigenomics Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Vicente Chapaprieta (V)

Biomedical Epigenomics Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Wenfei Sun (W)

Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.

Lourdes Navarro (L)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain.

Ignacio Prieto (I)

Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), 28029, Madrid, Spain.

Carlos Castaño (C)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain.

Anna Novials (A)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain.

Ramon Gomis (R)

Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain.

Maria Monsalve (M)

Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), 28029, Madrid, Spain.

Marc Claret (M)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Mariona Graupera (M)

Vascular Signalling Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907, Barcelona, Spain.

Guadalupe Soria (G)

Experimental 7T MRI Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Christian Wolfrum (C)

Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.

Joan Vendrell (J)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Institut d'Investigació Sanitària Pere Virgili, Endocrinology and Nutrition Service, Hospital Universitari de Tarragona Joan XXIII, 43007, Tarragona, Spain.

Sonia Fernández-Veledo (S)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Institut d'Investigació Sanitària Pere Virgili, Endocrinology and Nutrition Service, Hospital Universitari de Tarragona Joan XXIII, 43007, Tarragona, Spain.

Jose Antonio Enríquez (JA)

Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain, CIBERFES, 28029, Madrid, Spain.

Angel Carracedo (A)

Grupo de Medicina Xenómica, CIBERER, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, SERGAS, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.

José Carlos Perales (JC)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain; Nutrition, Metabolism and Gene Therapy Group; Diabetes and Metabolism Program; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.

Rubén Nogueiras (R)

Department of Physiology, CIMUS, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain.

Laura Herrero (L)

Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain; Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, 08028, Barcelona, Spain.

Aleksandra Trifunovic (A)

Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), and Institute for Mitochondrial Diseases and Ageing, Medical Faculty, University of Cologne, D-50931, Cologne, Germany.

Markus A Keller (MA)

Institute of Human Genetics, Medical University of Innsbruck, 6020, Innsbruck, Austria.

Oscar Yanes (O)

CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain; Department of Electronic Engineering, IISPV, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

Marta Sales-Pardo (M)

Department of Chemical Engineering, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

Roger Guimerà (R)

Department of Chemical Engineering, Universitat Rovira i Virgili, 43007, Tarragona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain.

Matthias Blüher (M)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Germany Liebigstr. 20, 4103, Leipzig, Germany.

José Ignacio Martín-Subero (JI)

Biomedical Epigenomics Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain; Department of Basic Clinical Practice, Universitat de Barcelona, 08036, Barcelona, Spain.

Pablo M Garcia-Roves (PM)

Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain; Nutrition, Metabolism and Gene Therapy Group; Diabetes and Metabolism Program; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain. Electronic address: pgarciaroves@ub.edu.

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