2026-04-29T04:08:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/51832024-09-27T07:56:41Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Soro-Arnaiz, Ines author Yang Li, Qilong Oscar author Torres-Capelli, Mar author Melendez-Rodriguez, Florinda author Veiga, Sonia author Veys, Koen author Sebastian, David author Elorza, Ainara author Tello, Daniel author Hernansanz-Agustin, Pablo author Cogliati, Sara author Moreno-Navarrete, Jose Maria author Balsa, Eduardo author Fuertes, Esther author Romanos, Eduardo author Martinez-Ruiz, Antonio author Enriquez, Jose Antonio author Fernandez-Real, Jose Manuel author Zorzano, Antonio author De Bock, Katrien author Aragones, Julian author 2016 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. Cell Rep. 2016; 16(11):2991-3002 2211-1247 http://hdl.handle.net/20.500.12105/5183 27626667 10.1016/j.celrep.2016.08.041 Cell Reports WHITE ADIPOSE-TISSUE CYTOCHROME-C-OXIDASE DIET-FED MICE INSULIN-RESISTANCE FAT HYPOXIA ADIPOCYTES DYSFUNCTION INFLAMMATION GLUCOSE Role of Mitochondrial Complex IV in Age-Dependent Obesity