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

González-Franquesa, A. ; Gama-Pérez, P. ; Kulis, M. ; Szczepanowska, K. ; Dahdah, N. ; Moreno-Gómez, S. ; Latorre Pellicer, A. (Universidad de Zaragoza) ; Fernández-Ruiz, R. ; Aguilar-Mogas, A. ; Hoffman, A. ; Monelli, E. ; Samino, S. ; Miró-Blanch, J. ; Oemer, G. ; Duran, X. ; Sánchez-Rebordelo, E. ; Schneeberger, M. ; Obach, M. ; Montane, J. ; Castellano, G. ; Chapaprieta, V. ; Sun, W. ; Navarro, L. ; Prieto, I. ; Castaño, C. ; Novials, A. ; Gomis, R. ; Monsalve, M. ; Claret, M. ; Graupera, M. ; Soria, G. ; Wolfrum, C. ; Vendrell, J. ; Fernández-Veledo, S. ; Enríquez, J. A. ; Carracedo, A. ; Perales, J. C. ; Nogueiras, R. ; Herrero, L. ; Trifunovic, A. ; Keller, M. A. ; Yanes, O. ; Sales-Pardo, M. ; Guimerà, R. ; Blüher, M. ; Martín-Subero, J. I. ; García-Roves, P.

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.redox.2022.102353

Año: 2022

Publicado en: Redox Biology 54 (2022), 102353 [18 pp.]
ISSN: 2213-2317

Factor impacto JCR: 11.4 (2022)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 20 / 285 = 0.07 (2022) - Q1 - T1

Factor impacto CITESCORE: 18.3 - Chemistry (Q1) - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 2.519 - Biochemistry (Q1) - Organic Chemistry (Q1) - Clinical Biochemistry (Q1)

Financiación: info:eu-repo/grantAgreement/ES/AEI/RTI2018-093864-B-I00
Financiación: info:eu-repo/grantAgreement/ES/AEI/SAF2017-83813-C3-1-R
Financiación: info:eu-repo/grantAgreement/EC/H2020/675610/EU/Chromatin and Metabolism Chromatin-metabolism interactions as targets for healthy living/ChroMe
Financiación: info:eu-repo/grantAgreement/EC/H2020/725004/EU/ Decoding mitochondrial nutrient-sensing programs in POMC neurons as key determinants of metabolic health/MITOSENSING
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI15-00701
Financiación: info:eu-repo/grantAgreement/ES/MICINN/BFU2011-24679
Financiación: info:eu-repo/grantAgreement/ES/MICINN-CIBERObn/CB06-03-0001
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2009-05158
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2013-062796
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2013-45887-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)