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

Redox Biology

Maria Monsalve¹  Laura Herrero²  Jose Antonio Enríquez²  José Carlos Perales²  Sara Samino²  Marc Schneeberger³  Joel Montane³  Erika Monelli⁴  Wenfei Sun⁵  Pablo M. Garcia-Roves⁵  Carlos Castaño⁶  Oscar Yanes⁷  Pau Gama-Perez⁸  Antoni Aguilar-Mogas⁹  Marc Claret^1,10  Karolina Szczepanowska^1,10  Mariona Graupera^1,10  Estrella Sanchez-Rebordelo^1,11  Merce Obach^1,11  José Ignacio Martín-Subero^1,11  Markus A. Keller^1,11  Vicente Chapaprieta^1,11  Norma Dahdah^1,12  Joan Miró-Blanch^1,13  Alba Gonzalez-Franquesa^1,14  Christian Wolfrum^1,14  Anne Hoffman^1,14  Sonia Moreno-Gomez^1,14  Marta Kulis^1,14  Ana Latorre-Pellicer^1,14  Lourdes Navarro^1,15  Sonia Fernández-Veledo^1,16  Ignacio Prieto^1,16  Anna Novials^1,16  Rubén Nogueiras^1,16  Ramon Gomis^1,16  Angel Carracedo^1,16  Roger Guimerà^1,17  Rebeca Fernández-Ruiz^1,18  Gregor Oemer^1,19  Matthias Blüher^2,20  Guadalupe Soria^2,20  Giancarlo Castellano^2,21  Aleksandra Trifunovic^2,22  Joan Vendrell^2,22  Xavier Duran^2,23  Marta Sales-Pardo^2,23 

[1] Blanquerna School of Health Science, Ramon Llull University, Barcelona, Spain;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;Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain;Institut d'Investigació Sanitària Pere Virgili, Endocrinology and Nutrition Service, Hospital Universitari de Tarragona Joan XXIII, 43007, Tarragona, Spain;Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, NY, 10065, New York, USA;Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain;Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark;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;Biomedical Epigenomics Group, 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;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;Department of Chemical Engineering, Universitat Rovira i Virgili, 43007, Tarragona, Spain;Department of Physiological Sciences, Universitat de Barcelona, 08907, Barcelona, Spain;Department of Physiology, CIMUS, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain;Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain;Experimental 7T MRI Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;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;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;Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland;Institute of Human Genetics, Medical University of Innsbruck, 6020, Innsbruck, Austria;Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), 28029, Madrid, Spain;Vascular Signalling Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907, Barcelona, Spain;

关键词: Obesity;    Metabolic plasticity;    Visceral adipose tissue;    Mitochondrial dysfunction;    Exercise;    Caloric restriction;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown