p66Shc-generated oxidative signal promotes fat accumulation.
J Biol Chem
; 283(49): 34283-93, 2008 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-18838380
ABSTRACT
Reactive oxygen species (ROS) and insulin signaling in the adipose tissue are critical determinants of aging and age-associated diseases. It is not clear, however, if they represent independent factors or they are mechanistically linked. We investigated the effects of ROS on insulin signaling using as model system the p66(Shc)-null mice. p66(Shc) is a redox enzyme that generates mitochondrial ROS and promotes aging in mammals. We report that insulin activates the redox enzyme activity of p66(Shc) specifically in adipocytes and that p66(Shc)-generated ROS regulate insulin signaling through multiple mechanisms, including AKT phosphorylation, Foxo localization, and regulation of selected insulin target genes. Deletion of p66(Shc) resulted in increased mitochondrial uncoupling and reduced triglyceride accumulation in adipocytes and in vivo increased metabolic rate and decreased fat mass and resistance to diet-induced obesity. In addition, p66(Shc-/-) mice showed impaired thermo-insulation. These findings demonstrate that p66(Shc)-generated ROS regulate the effect of insulin on the energetic metabolism in mice and suggest that intracellular oxidative stress might accelerate aging by favoring fat deposition and fat-related disorders.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estresse Oxidativo
/
Proteínas Adaptadoras da Sinalização Shc
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália