c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action
Casitas b-lineage lymphoma (c-Cbl) is an E3 ubiquitin ligase that has an important role in regulating the degradation of cell surface receptors. In the present study we have examined the role of c-Cbl in whole-body energy homeostasis. c-Cbl-/- mice exhibited a profound increase in whole-body energy expenditure as determined by increased core temperature and whole-body oxygen consumption. As a consequence, these mice displayed a decrease in adiposity, primarily due to a reduction in cell size despite an increase in food intake. These changes were accompanied by a significant increase in activity (2- to 3-fold). In addition, c-Cbl-/- mice displayed a marked improvement in whole-body insulin action, primarily due to changes in muscle metabolism. We observed increased protein levels of the insulin receptor (4-fold) and uncoupling protein-3 (2-fold) in skeletal muscle and a significant increase in the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. These findings suggest that c-Cbl plays an integral role in whole-body fuel homeostasis by regulating whole-body energy expenditure and insulin action.
|Authors||Molero, J. C.;Jensen, T. E.;Withers, P. C.;Couzens, M.;Herzog, H.;Thien, C. B.;Langdon, W. Y.;Walder, K.;Murphy, M. A.;Bowtell, D. D.;James, D. E.;Cooney, G. J. :|
|Publisher Name||JOURNAL OF CLINICAL INVESTIGATION|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15520865|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/1824|