Role of Mitochondrial Complex IV in Age-Dependent Obesity.

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve...

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Autores: Soro-Arnaiz, Ines, Yang Li, Qilong Oscar, Torres-Capelli, Mar, Meléndez-Rodríguez, Florinda, Veiga, Sonia Rosa Pereira da, Veys, Koen, Sebastián Muñoz, David, Elorza, Ainara, Tello Velasco, Daniel, Hernansanz Agustín, Pablo, Cogliati, Sara, Moreno-Navarrete, José María, Balsa, Eduardo, Fuertes, Esther, Romanos, Eduardo, Martínez Ruiz, Antonio, Enriquez, Jose Antonio, Fernández-Real Lemos, José Manuel, Zorzano Olarte, Antonio, De Bock, Katrien, Aragonés, Julián
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/114790
Acceso en línea:https://hdl.handle.net/2445/114790
Access Level:acceso abierto
Palabra clave:Envelliment
Obesitat
ADN mitocondrial
Aging
Obesity
Mitochondrial DNA
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repository_id_str
spelling Role of Mitochondrial Complex IV in Age-Dependent Obesity.Soro-Arnaiz, InesYang Li, Qilong OscarTorres-Capelli, MarMeléndez-Rodríguez, FlorindaVeiga, Sonia Rosa Pereira daVeys, KoenSebastián Muñoz, DavidElorza, AinaraTello Velasco, DanielHernansanz Agustín, PabloCogliati, SaraMoreno-Navarrete, José MaríaBalsa, EduardoFuertes, EstherRomanos, EduardoMartínez Ruiz, AntonioEnriquez, Jose AntonioFernández-Real Lemos, José ManuelZorzano Olarte, AntonioDe Bock, KatrienAragonés, JuliánEnvellimentObesitatADN mitocondrialAgingObesityMitochondrial DNAAging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.Elsevier2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/114790Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2016.08.041Cell Reports, 2016https://doi.org/10.1016/j.celrep.2016.08.041info:eu-repo/grantAgreement/EC/FP7/282551cc-by (c) Soro-Arnaiz, Ines et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1147902026-05-27T06:46:51Z
dc.title.none.fl_str_mv Role of Mitochondrial Complex IV in Age-Dependent Obesity.
title Role of Mitochondrial Complex IV in Age-Dependent Obesity.
spellingShingle Role of Mitochondrial Complex IV in Age-Dependent Obesity.
Soro-Arnaiz, Ines
Envelliment
Obesitat
ADN mitocondrial
Aging
Obesity
Mitochondrial DNA
title_short Role of Mitochondrial Complex IV in Age-Dependent Obesity.
title_full Role of Mitochondrial Complex IV in Age-Dependent Obesity.
title_fullStr Role of Mitochondrial Complex IV in Age-Dependent Obesity.
title_full_unstemmed Role of Mitochondrial Complex IV in Age-Dependent Obesity.
title_sort Role of Mitochondrial Complex IV in Age-Dependent Obesity.
dc.creator.none.fl_str_mv Soro-Arnaiz, Ines
Yang Li, Qilong Oscar
Torres-Capelli, Mar
Meléndez-Rodríguez, Florinda
Veiga, Sonia Rosa Pereira da
Veys, Koen
Sebastián Muñoz, David
Elorza, Ainara
Tello Velasco, Daniel
Hernansanz Agustín, Pablo
Cogliati, Sara
Moreno-Navarrete, José María
Balsa, Eduardo
Fuertes, Esther
Romanos, Eduardo
Martínez Ruiz, Antonio
Enriquez, Jose Antonio
Fernández-Real Lemos, José Manuel
Zorzano Olarte, Antonio
De Bock, Katrien
Aragonés, Julián
author Soro-Arnaiz, Ines
author_facet Soro-Arnaiz, Ines
Yang Li, Qilong Oscar
Torres-Capelli, Mar
Meléndez-Rodríguez, Florinda
Veiga, Sonia Rosa Pereira da
Veys, Koen
Sebastián Muñoz, David
Elorza, Ainara
Tello Velasco, Daniel
Hernansanz Agustín, Pablo
Cogliati, Sara
Moreno-Navarrete, José María
Balsa, Eduardo
Fuertes, Esther
Romanos, Eduardo
Martínez Ruiz, Antonio
Enriquez, Jose Antonio
Fernández-Real Lemos, José Manuel
Zorzano Olarte, Antonio
De Bock, Katrien
Aragonés, Julián
author_role author
author2 Yang Li, Qilong Oscar
Torres-Capelli, Mar
Meléndez-Rodríguez, Florinda
Veiga, Sonia Rosa Pereira da
Veys, Koen
Sebastián Muñoz, David
Elorza, Ainara
Tello Velasco, Daniel
Hernansanz Agustín, Pablo
Cogliati, Sara
Moreno-Navarrete, José María
Balsa, Eduardo
Fuertes, Esther
Romanos, Eduardo
Martínez Ruiz, Antonio
Enriquez, Jose Antonio
Fernández-Real Lemos, José Manuel
Zorzano Olarte, Antonio
De Bock, Katrien
Aragonés, Julián
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Envelliment
Obesitat
ADN mitocondrial
Aging
Obesity
Mitochondrial DNA
topic Envelliment
Obesitat
ADN mitocondrial
Aging
Obesity
Mitochondrial DNA
description Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/114790
url https://hdl.handle.net/2445/114790
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2016.08.041
Cell Reports, 2016
https://doi.org/10.1016/j.celrep.2016.08.041
info:eu-repo/grantAgreement/EC/FP7/282551
dc.rights.none.fl_str_mv cc-by (c) Soro-Arnaiz, Ines et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Soro-Arnaiz, Ines et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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