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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Detalhes bibliográficos
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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/114790
Acesso em linha:https://hdl.handle.net/2445/114790
Access Level:acceso abierto
Palavra-chave:Envelliment
Obesitat
ADN mitocondrial
Aging
Obesity
Mitochondrial DNA
Descrição
Resumo: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.

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