TY - JOUR
T1 - Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue
AU - Gonzalez-Franquesa, Alba
AU - Gama-Perez, Pau
AU - Kulis, Marta
AU - Szczepanowska, Karolina
AU - Dahdah, Norma
AU - Moreno-Gomez, Sonia
AU - Latorre-Pellicer, Ana
AU - Fernández-Ruiz, Rebeca
AU - Aguilar-Mogas, Antoni
AU - Hoffman, Anne
AU - Monelli, Erika
AU - Samino, Sara
AU - Miró-Blanch, Joan
AU - Oemer, Gregor
AU - Duran, Xavier
AU - Sanchez-Rebordelo, Estrella
AU - Schneeberger, Marc
AU - Obach, Merce
AU - Montane, Joel
AU - Castellano, Giancarlo
AU - Chapaprieta, Vicente
AU - Sun, Wenfei
AU - Navarro, Lourdes
AU - Prieto, Ignacio
AU - Castaño, Carlos
AU - Novials, Anna
AU - Gomis, Ramon
AU - Monsalve, Maria
AU - Claret, Marc
AU - Graupera, Mariona
AU - Soria, Guadalupe
AU - Wolfrum, Christian
AU - Vendrell, Joan
AU - Fernández-Veledo, Sonia
AU - Enríquez, Jose Antonio
AU - Carracedo, Angel
AU - Perales, José Carlos
AU - Nogueiras, Rubén
AU - Herrero, Laura
AU - Trifunovic, Aleksandra
AU - Keller, Markus A.
AU - Yanes, Oscar
AU - Sales-Pardo, Marta
AU - Guimerà, Roger
AU - Blüher, Matthias
AU - Martín-Subero, José Ignacio
AU - Garcia-Roves, Pablo M.
N1 - Funding Information:
This work has been supported by Ministerio de Ciencia e Innovación (MICINN) Grant BFU2011- 24679 (P.M.G.-R.); Instituto de Salud Carlos III (ISCIII) Grant PI15/00701 (P.M.G.-R.) cofinanced by the European Regional Development Fund ‘‘A way to build Europe’‘; Government of Catalonia Support Grups de Recerca AGAUR 2017-SGR-204 (to J.C.P. and P.M.G-R.), 2017-SGR-736 (to J.I.M.-S.) and 2017-SGR-896 (to A.A.-M. M.S.-P. and R.G.). M.M. was recipient of a MINECO grant RTI2018-093864-B-I00. O.Y. was funded by MINECO grant BFU2017-87958. M.A.K. was funded by a Medical University of Innsbruck Start Grant. M.C. was funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement 725004). L. H. was funded by MINECO grants SAF2013-45887-R, SAF2017-83813-C3-1-R (granted to Dolors Serra (DS) and L.H.), co-funded by the European Regional Development Fund, the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (Grant CB06/03/0001 to DS), the Government of Catalonia (2017SGR278 to DS), the Fundació La Marató de TV3 (201627–30 to DS), the European Foundation for the Study of Diabetes (EFSD)/Janssen-Rising Star and L'Oréal-UNESCO “For Women in Science” research fellowships. P.M.G.-R. was a recipient of a Ramon y Cajal contract (RYC-2009-05158) from MICINN. A.G-F. was a recipient of “Beca de Formació de Personal Investigador de l'IDIBAPS” fellowship and she is currently supported by an unconditional donation from the Novo Nordisk Foundation (NNF) to NNF Center for Basic Metabolic Research (NNF18CC0034900). P.G-P. was a recipient of predoctoral fellowship from the Universitat de Barcelona (APIF-UB). K.S was financed through “Advanced Postdoc Grant” from SFB 1218 (DFG, German Reuter Foundation, Projektnummer 269925409). J.M-B. was a recipient of predoctoral fellowship from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 675610. E.S-R. was recipient of a predoctoral fellowship from Ministerio de Economia y Empresa (MINECO) grant BES-2013-062796. This work was partially developed at the Esther Koplowitz Center (CEK, Barcelona, Spain). We want to acknowledge the following experts: Drs. Vidal-Puig A. Malagon M.M. and Raimundo N. for their advice and critical discussion of our work.
Funding Information:
This work has been supported by Ministerio de Ciencia e Innovación (MICINN) Grant BFU2011- 24679 (P.M.G.-R.); Instituto de Salud Carlos III (ISCIII) Grant PI15/00701 (P.M.G.-R.) cofinanced by the European Regional Development Fund ‘‘A way to build Europe’‘; Government of Catalonia Support Grups de Recerca AGAUR 2017-SGR-204 (to J.C.P. and P.M.G-R.), 2017-SGR-736 (to J.I.M.-S.) and 2017-SGR-896 (to A.A.-M., M.S.-P., and R.G.). M.M. was recipient of a MINECO grant RTI2018-093864-B-I00. O.Y. was funded by MINECO grant BFU2017-87958 . M.A.K. was funded by a Medical University of Innsbruck Start Grant. M.C. was funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement 725004 ). L. H. was funded by MINECO grants SAF2013-45887-R , SAF2017-83813-C3-1-R (granted to Dolors Serra (DS) and L.H.), co-funded by the European Regional Development Fund , the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (Grant CB06/03/0001 to DS), the Government of Catalonia ( 2017SGR278 to DS), the Fundació La Marató de TV3 ( 201627–30 to DS), the European Foundation for the Study of Diabetes (EFSD)/ Janssen-Rising Star and L’Oréal-UNESCO “For Women in Science” research fellowships. P.M.G.-R. was a recipient of a Ramon y Cajal contract ( RYC-2009-05158 ) from MICINN . A.G-F. was a recipient of “ Beca de Formació de Personal Investigador de l'IDIBAPS ” fellowship and she is currently supported by an unconditional donation from the Novo Nordisk Foundation (NNF) to NNF Center for Basic Metabolic Research ( NNF18CC0034900 ). P.G-P. was a recipient of predoctoral fellowship from the Universitat de Barcelona (APIF-UB). K.S was financed through “ Advanced Postdoc Grant ” from SFB 1218 ( DFG, German Reuter Foundation , Projektnummer 269925409 ). J.M-B. was a recipient of predoctoral fellowship from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 675610 . E.S-R. was recipient of a predoctoral fellowship from Ministerio de Economia y Empresa (MINECO) grant BES-2013-062796 . This work was partially developed at the Esther Koplowitz Center (CEK, Barcelona, Spain). We want to acknowledge the following experts: Drs. Vidal-Puig A., Malagon M.M. and Raimundo N. for their advice and critical discussion of our work.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/8
Y1 - 2022/8
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, 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.
AB - 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.
KW - Caloric restriction
KW - Exercise
KW - Human obesity
KW - Metabolic fingerprint
KW - Metabolic plasticity
KW - Mitochondrial dysfunction
KW - Multi-organ approach
KW - Obesity
KW - Two-steps bariatric surgery
KW - Visceral adipose tissue
UR - http://www.scopus.com/inward/record.url?scp=85133597848&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000861768000002&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.redox.2022.102353
DO - 10.1016/j.redox.2022.102353
M3 - Article
C2 - 35777200
AN - SCOPUS:85133597848
SN - 2213-2317
VL - 54
JO - Redox Biology
JF - Redox Biology
M1 - 102353
ER -
