Genetic albation of the c-Cbl ubiquitin ligase domain results in increased energy expenditure and improved insulin action
Data(s) |
01/01/2006
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Resumo |
Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity residing within its RING finger domain. We have previously reported that c-Cbl–deficient mice exhibit elevated energy expenditure, reduced adiposity, and improved insulin action. In this study, we examined mice expressing c-Cbl protein with a loss-of-function mutation within the RING finger domain (c-Cbl<sup>A/–</sup> mice). Compared with control animals, c-Cbl<sup>A/–</sup> mice display a phenotype that includes reduced adiposity, despite greater food intake; reduced circulating insulin, leptin, and triglyceride levels; and improved glucose tolerance. c-Cbl<sup>A/–</sup> mice also display elevated oxygen consumption (13%) and are protected against high-fat diet–induced obesity and insulin resistance. Unlike c-Cbl<sup>A/–</sup> mice, mice expressing a mutant c-Cbl with the phosphatidylinositol (PI) 3-kinase binding domain ablated (c-Cbl<sup>F/F</sup> mice) exhibited an insulin sensitivity, body composition, and energy expenditure similar to that of wild-type animals. These results indicate that c-Cbl ubiquitin ligase activity, but not c-Cbl–dependent activation of PI 3-kinase, plays a key role in the regulation of whole-body energy metabolism.<br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
American Diabetes Association |
Relação |
http://dro.deakin.edu.au/eserv/DU:30004146/molero-geneticalbation-2006.pdf http://dx.doi.org/10.2337/db06-0955 |
Direitos |
2006, American Diabetes Association |
Tipo |
Journal Article |