Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.08.194167v1?rss=1 Authors: Alba Gonzalez-Franquesa, Pau Gama-Perez, Marta Kulis, Norma Dahdah, Sonia Moreno-Gomez, Ana Latorre-Pellicer, Rebeca Fernandez-Ruiz, Antoni Aguilar-Mogas, Erika Monelli, Sara Samino, Joan Miro, Gregor Oemer, Xavier Duran, Estrella Sanchez-Rebordelo, Marc Schneeberger, Merce Obach, Joel Montane, Giancarlo Castellano, Vicente Chapaprieta, Lourdes Navarro, Ignacio Prieto, Carlos Castano, Anna Novials, Ramon Gomis, Maria Monsalve, Marc Claret, Mariona Graupera, Guadalupe Soria, Joan Vendrell, Sonia Fernandez-Veledo, Jose Antonio Enriquez, Angel Carracedo, Jose Carlos Perales, Ruben Nogueiras, Laur Abstract: 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. Copy rights belong to original authors. Visit the link for more info