c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action
Molero, Juan Carlos, Jensen, Thomas E., Withers, Phil C., Couzens, Michelle, Herzog, Herbert, Thien, Christine B.F., Langdon, Wallace Y., Walder, Ken, Murphy, Maria A., Bowtell, David D.L., James, David E. and Cooney, Gregory J. 2004, c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action, Journal of clinical investigation, vol. 114, no. 9, pp. 1326-1333.
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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-Cb-/- 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, cc-Cb-/- 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 fmdings suggest that c-Cbl plays an integral role in whole-body fuel homeostasis by regulating whole-body energy expenditure and insulin action.
Field of Research
060405 Gene Expression (incl Microarray and other genome-wide approaches)
Socio Economic Objective
970106 Expanding Knowledge in the Biological Sciences
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