000057077 001__ 57077 000057077 005__ 20200221144222.0 000057077 0247_ $$2doi$$a10.1016/j.celrep.2016.08.041 000057077 0248_ $$2sideral$$a96685 000057077 037__ $$aART-2016-96685 000057077 041__ $$aeng 000057077 100__ $$aSoro-Arnaiz, I. 000057077 245__ $$aRole of Mitochondrial Complex IV in Age-Dependent Obesity 000057077 260__ $$c2016 000057077 5060_ $$aAccess copy available to the general public$$fUnrestricted 000057077 5203_ $$aAging 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. 000057077 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2013-46058-R$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2011-29716$$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0065$$9info:eu-repo/grantAgreement/EC/FP7/282551/EU/Gaining sage on the Epoetins' saga: assessing long term risks and advancing towards better Epoetin driven treatment modalities/EPOCAN$$9info:eu-repo/grantAgreement/ES/CICYT/SAF2007-60592$$9info:eu-repo/grantAgreement/ES/CAM/P2010-BMD-2542 000057077 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000057077 590__ $$a8.282$$b2016 000057077 591__ $$aCELL BIOLOGY$$b26 / 189 = 0.138$$c2016$$dQ1$$eT1 000057077 592__ $$a8.336$$b2016 000057077 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1 000057077 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000057077 700__ $$aLi, Q.O.Y. 000057077 700__ $$aTorres-Capelli, M. 000057077 700__ $$aMeléndez-Rodríguez, F. 000057077 700__ $$aVeiga, S. 000057077 700__ $$aVeys, K. 000057077 700__ $$aSebastian, D. 000057077 700__ $$aElorza, A. 000057077 700__ $$aTello, D. 000057077 700__ $$aHernansanz-Agustín, P. 000057077 700__ $$aCogliati, S. 000057077 700__ $$aMoreno-Navarrete, J. 000057077 700__ $$aBalsa, E. 000057077 700__ $$aFuertes, E. 000057077 700__ $$aRomanos, E. 000057077 700__ $$aMartínez-Ruiz, A. 000057077 700__ $$aEnriquez, J.A. 000057077 700__ $$aFernandez-Real, J. 000057077 700__ $$aZorzano, A. 000057077 700__ $$aDe Bock, K. 000057077 700__ $$aAragonés, J. 000057077 773__ $$g16, 11 (2016), 2991-3002$$pCell Reports$$tCell Reports$$x2211-1247 000057077 8564_ $$s884710$$uhttps://zaguan.unizar.es/record/57077/files/texto_completo.pdf$$yVersión publicada 000057077 8564_ $$s120053$$uhttps://zaguan.unizar.es/record/57077/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000057077 909CO $$ooai:zaguan.unizar.es:57077$$particulos$$pdriver 000057077 951__ $$a2020-02-21-13:15:40 000057077 980__ $$aARTICLE