TY - JOUR T1 - Obesity causes irreversible mitochondria failure in visceral adipose tissue despite successful anti-obesogenic lifestyle-based interventions JF - bioRxiv DO - 10.1101/2020.07.08.194167 SP - 2020.07.08.194167 AU - Alba Gonzalez-Franquesa AU - Pau Gama-Perez AU - Marta Kulis AU - Norma Dahdah AU - Sonia Moreno-Gomez AU - Ana Latorre-Pellicer AU - Rebeca Fernández-Ruiz AU - Antoni Aguilar-Mogas AU - Erika Monelli AU - Sara Samino AU - Joan Miró AU - Gregor Oemer AU - Xavier Duran AU - Estrella Sanchez-Rebordelo AU - Marc Schneeberger AU - Merce Obach AU - Joel Montane AU - Giancarlo Castellano AU - Vicente Chapaprieta AU - Lourdes Navarro AU - Ignacio Prieto AU - Carlos Castaño AU - Anna Novials AU - Ramon Gomis AU - Maria Monsalve AU - Marc Claret AU - Mariona Graupera AU - Guadalupe Soria AU - Joan Vendrell AU - Sonia Fernandez-Veledo AU - Jose Antonio Enríquez AU - Angel Carracedo AU - José Carlos Perales AU - Rubén Nogueiras AU - Laura Herrero AU - Markus A. Keller AU - Oscar Yanes AU - Marta Sales-Pardo AU - Roger Guimerà AU - José Ignacio Martín-Subero AU - Pablo M. Garcia-Roves Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/11/2020.07.08.194167.abstract N2 - 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, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most pathological features were successfully reverted, we observed a high degree of metabolic dysfunction irreversibility in visceral white adipose tissue, characterised by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and apparent global phenotypic recovery, obesity specifically triggered in visceral adipose a cascade of events progressing from mitochondrial metabolic and proteostatic defects to widespread cellular stress, which compromises its biosynthetic and recycling capacity. Our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in white adipose tissue, becoming a significant milestone in disease progression.Competing Interest StatementThe authors have declared no competing interest. ER -