Title: Role of Mitochondrial Complex IV in Age-Dependent Obesity
Authors: Soro-Arnaiz, Ines *
Li, Qilong Oscar Yang *
Torres-Capelli, Mar
Meléndez-Rodríguez, Florinda
Veiga, Sónia
Veys, Koen
Sebastian, David
Elorza, Ainara
Tello, Daniel
Hernansanz-Agustín, Pablo
Cogliati, Sara
Moreno-Navarrete, Jose Maria
Balsa, Eduardo
Fuertes, Esther
Romanos, Eduardo
Martínez-Ruiz, Antonio
Enriquez, Jose Antonio
Fernandez-Real, Jose Manuel
Zorzano, Antonio
De Bock, Katrien
Aragonés, Julián # ×
Issue Date: 13-Sep-2016
Publisher: Elsevier Inc
Series Title: Cell Reports vol:16 issue:11 pages:2991-3002
Article number: 10.1016/j.celrep.2016.08.041
Abstract: 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.
ISSN: 2211-1247
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Exercise Physiology Research Group
* (joint) first author
× corresponding author
# (joint) last author

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