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

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-...

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Detalles Bibliográficos
Autores: González-Franquesa, Alba, Gama-Pérez, Pau, Kulis, Marta, Szczepanowska, Karolina, Dahdah, Norma, Moreno-Gomez, Sonia, Latorre-Pellicer, Ana, Fernández-Ruiz, Rebeca, Aguilar-Mogas, Antoni, Hoffman, Anne, Monelli, Erika, Samino, Sara, Miró-Blanch, Joan, Oemer, Gregor, Durán, Xavier, Sanchez-Rebordelo, Estrella, Schneeberger, Marc, Obach, Merce, Montane, Joel, Castellano, Giancarlo, Chapaprieta, Vicente, Sun, Wenfei, Navarro, Lourdes, Prieto, Ignacio, Castaño, Carlos, Novials, Anna, Gomis, Ramón, Monsalve, María, Claret, Marc, Graupera, Mariona, Soria, Guadalupe, Wolfrum, Christian, Vendrell, Joan, Fernández-Veledo, Sonia, Enríquez, José Antonio, Perales, José Carlos, Nogueiras, Rubén, Herrero, Laura, Trifunovic, Aleksandra, Keller, Markus A., Yanes, Óscar, Sales-Pardo, Marta, Guimerà, Roger, Blüher, Matthias, Martín-Subero, José Ignacio, Garcia-Roves, Pablo M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::7ed539664c29a36f87581ab2987b7600
Acceso en línea:http://hdl.handle.net/10261/290334
Access Level:acceso abierto
Palabra clave:Obesity
Metabolic plasticity
Visceral adipose tissue
Mitochondrial dysfunction
Exercise
Caloric restriction
Multi-organ approach
Human obesity
Two-steps bariatric surgery
Metabolic fingerprint
Descripción
Sumario: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.

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