Gonzalez-Franquesa, A.* ; Gama-Perez, P.* ; Kulis, M.* ; Szczepanowska, K.* ; Dahdah, N.* ; Moreno-Gomez, S.* ; Latorre-Pellicer, A.* ; Fernández-Ruiz, R.* ; Aguilar-Mogas, A.* ; Hoffmann, A. ; Monelli, E.* ; Samino, S.* ; Miró-Blanch, J.* ; Oemer, G.* ; Duran, X.* ; Sanchez-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.* ; Garcia-Roves, P.M.*
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue.
Redox Biol. 54:102353 (2022)
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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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Caloric Restriction ; Exercise ; Human Obesity ; Metabolic Fingerprint ; Metabolic Plasticity ; Mitochondrial Dysfunction ; Multi-organ Approach ; Obesity ; Two-steps Bariatric Surgery ; Visceral Adipose Tissue
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Language
english
Publication Year
2022
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2022
ISSN (print) / ISBN
2213-2317
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2213-2317
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Article Number: 102353
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Elsevier
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Amsterdam [u.a.]
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Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-506501-001
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Erfassungsdatum
2022-11-02