Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue
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-...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:dnet:digitalcsic_::7ed539664c29a36f87581ab2987b7600 |
| Acesso em linha: | http://hdl.handle.net/10261/290334 |
| Access Level: | acceso abierto |
| Palavra-chave: | Obesity Metabolic plasticity Visceral adipose tissue Mitochondrial dysfunction Exercise Caloric restriction Multi-organ approach Human obesity Two-steps bariatric surgery Metabolic fingerprint |
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Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| title |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| spellingShingle |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue González-Franquesa, Alba Obesity Metabolic plasticity Visceral adipose tissue Mitochondrial dysfunction Exercise Caloric restriction Multi-organ approach Human obesity Two-steps bariatric surgery Metabolic fingerprint |
| title_short |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| title_full |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| title_fullStr |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| title_full_unstemmed |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| title_sort |
Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue |
| dc.creator.none.fl_str_mv |
González-Franquesa, Alba Gama-Pérez, Pau Kulis, Marta Szczepanowska, Karolina Dahdah, Norma Moreno-Gomez, Sonia Latorre-Pellicer, Ana Fernández-Ruiz, Rebeca Aguilar-Mogas, Antoni Hoffman, Anne Monelli, Erika Samino, Sara Miró-Blanch, Joan Oemer, Gregor Durán, Xavier Sanchez-Rebordelo, Estrella Schneeberger, Marc Obach, Merce Montane, Joel Castellano, Giancarlo Chapaprieta, Vicente Sun, Wenfei Navarro, Lourdes Prieto, Ignacio Castaño, Carlos Novials, Anna Gomis, Ramón Monsalve, María Claret, Marc Graupera, Mariona Soria, Guadalupe Wolfrum, Christian Vendrell, Joan Fernández-Veledo, Sonia Enríquez, José Antonio Perales, José Carlos Nogueiras, Rubén Herrero, Laura Trifunovic, Aleksandra Keller, Markus A. Yanes, Óscar Sales-Pardo, Marta Guimerà, Roger Blüher, Matthias Martín-Subero, José Ignacio Garcia-Roves, Pablo M. |
| author |
González-Franquesa, Alba |
| author_facet |
González-Franquesa, Alba Gama-Pérez, Pau Kulis, Marta Szczepanowska, Karolina Dahdah, Norma Moreno-Gomez, Sonia Latorre-Pellicer, Ana Fernández-Ruiz, Rebeca Aguilar-Mogas, Antoni Hoffman, Anne Monelli, Erika Samino, Sara Miró-Blanch, Joan Oemer, Gregor Durán, Xavier Sanchez-Rebordelo, Estrella Schneeberger, Marc Obach, Merce Montane, Joel Castellano, Giancarlo Chapaprieta, Vicente Sun, Wenfei Navarro, Lourdes Prieto, Ignacio Castaño, Carlos Novials, Anna Gomis, Ramón Monsalve, María Claret, Marc Graupera, Mariona Soria, Guadalupe Wolfrum, Christian Vendrell, Joan Fernández-Veledo, Sonia Enríquez, José Antonio Perales, José Carlos Nogueiras, Rubén Herrero, Laura Trifunovic, Aleksandra Keller, Markus A. Yanes, Óscar Sales-Pardo, Marta Guimerà, Roger Blüher, Matthias Martín-Subero, José Ignacio Garcia-Roves, Pablo M. |
| author_role |
author |
| author2 |
Gama-Pérez, Pau Kulis, Marta Szczepanowska, Karolina Dahdah, Norma Moreno-Gomez, Sonia Latorre-Pellicer, Ana Fernández-Ruiz, Rebeca Aguilar-Mogas, Antoni Hoffman, Anne Monelli, Erika Samino, Sara Miró-Blanch, Joan Oemer, Gregor Durán, Xavier Sanchez-Rebordelo, Estrella Schneeberger, Marc Obach, Merce Montane, Joel Castellano, Giancarlo Chapaprieta, Vicente Sun, Wenfei Navarro, Lourdes Prieto, Ignacio Castaño, Carlos Novials, Anna Gomis, Ramón Monsalve, María Claret, Marc Graupera, Mariona Soria, Guadalupe Wolfrum, Christian Vendrell, Joan Fernández-Veledo, Sonia Enríquez, José Antonio Perales, José Carlos Nogueiras, Rubén Herrero, Laura Trifunovic, Aleksandra Keller, Markus A. Yanes, Óscar Sales-Pardo, Marta Guimerà, Roger Blüher, Matthias Martín-Subero, José Ignacio Garcia-Roves, Pablo M. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia, Innovación y Universidades (España) Agencia Estatal de Investigación (España) Instituto de Salud Carlos III Generalitat de Catalunya Ministerio de Economía y Competitividad (España) Fundació La Marató de TV3 European Foundation for the Study of Diabetes Novo Nordisk Foundation European Commission Centro Esther Koplowitz Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Obesity Metabolic plasticity Visceral adipose tissue Mitochondrial dysfunction Exercise Caloric restriction Multi-organ approach Human obesity Two-steps bariatric surgery Metabolic fingerprint |
| topic |
Obesity Metabolic plasticity Visceral adipose tissue Mitochondrial dysfunction Exercise Caloric restriction Multi-organ approach Human obesity Two-steps bariatric surgery Metabolic fingerprint |
| description |
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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/290334 |
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http://hdl.handle.net/10261/290334 |
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Inglés |
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Inglés |
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Elsevier |
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Elsevier |
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Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissueGonzález-Franquesa, AlbaGama-Pérez, PauKulis, MartaSzczepanowska, KarolinaDahdah, NormaMoreno-Gomez, SoniaLatorre-Pellicer, AnaFernández-Ruiz, RebecaAguilar-Mogas, AntoniHoffman, AnneMonelli, ErikaSamino, SaraMiró-Blanch, JoanOemer, GregorDurán, XavierSanchez-Rebordelo, EstrellaSchneeberger, MarcObach, MerceMontane, JoelCastellano, GiancarloChapaprieta, VicenteSun, WenfeiNavarro, LourdesPrieto, IgnacioCastaño, CarlosNovials, AnnaGomis, RamónMonsalve, MaríaClaret, MarcGraupera, MarionaSoria, GuadalupeWolfrum, ChristianVendrell, JoanFernández-Veledo, SoniaEnríquez, José AntonioPerales, José CarlosNogueiras, RubénHerrero, LauraTrifunovic, AleksandraKeller, Markus A.Yanes, ÓscarSales-Pardo, MartaGuimerà, RogerBlüher, MatthiasMartín-Subero, José IgnacioGarcia-Roves, Pablo M.ObesityMetabolic plasticityVisceral adipose tissueMitochondrial dysfunctionExerciseCaloric restrictionMulti-organ approachHuman obesityTwo-steps bariatric surgeryMetabolic fingerprintMetabolic 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.This work has been supported by Ministerio de Ciencia e Innovacion ´ (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 Investigacion ´ Biom´edica en Red de Fisiopatología de la Obesidad y la Nutricion ´ (CIBEROBN) (Grant CB06/03/0001 to DS), the Government of Catalonia (2017SGR278 to DS), the Fundacio ´ La Marato ´ de TV3 (201627–30 to DS), the European Foundation for the Study of Diabetes (EFSD)/Janssen-Rising Star and L’Or´eal-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 Formacio ´ 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 SkłodowskaCurie 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).ElsevierMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIGeneralitat de CatalunyaMinisterio de Economía y Competitividad (España)Fundació La Marató de TV3European Foundation for the Study of DiabetesNovo Nordisk FoundationEuropean CommissionCentro Esther KoplowitzConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/290334reponame:DIGITAL.CSIC. 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