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

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  • Alba Gonzalez-Franquesa
  • Pau Gama-Perez
  • Marta Kulis
  • Karolina Szczepanowska
  • Norma Dahdah
  • Sonia Moreno-Gomez
  • Ana Latorre-Pellicer
  • Rebeca Fernández-Ruiz
  • Antoni Aguilar-Mogas
  • Anne Hoffman
  • Erika Monelli
  • Sara Samino
  • Joan Miró-Blanch
  • Gregor Oemer
  • Xavier Duran
  • Estrella Sanchez-Rebordelo
  • Marc Schneeberger
  • Merce Obach
  • Joel Montane
  • Giancarlo Castellano
  • And 27 others
  • Vicente Chapaprieta
  • Wenfei Sun
  • Lourdes Navarro
  • Ignacio Prieto
  • Carlos Castaño
  • Anna Novials
  • Ramon Gomis
  • Maria Monsalve
  • Marc Claret
  • Mariona Graupera
  • Guadalupe Soria
  • Christian Wolfrum
  • Joan Vendrell
  • Sonia Fernández-Veledo
  • Jose Antonio Enríquez
  • Angel Carracedo
  • José Carlos Perales
  • Rubén Nogueiras
  • Laura Herrero
  • Aleksandra Trifunovic
  • Markus A. Keller
  • Oscar Yanes
  • Marta Sales-Pardo
  • Roger Guimerà
  • Matthias Blüher
  • José Ignacio Martín-Subero
  • Pablo M. Garcia-Roves

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.

Original languageEnglish
Article number102353
JournalRedox Biology
Number of pages18
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

    Research areas

  • Caloric restriction, Exercise, Human obesity, Metabolic fingerprint, Metabolic plasticity, Mitochondrial dysfunction, Multi-organ approach, Obesity, Two-steps bariatric surgery, Visceral adipose tissue

ID: 314440782