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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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Title c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action
Author(s) 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.
Cooney, Gregory J.
Journal name Journal of clinical investigation
Volume number 114
Issue number 9
Start page 1326
End page 1333
Publisher American Society for Clinical Investigation
Place of publication New York, N.Y.
Publication date 2004-11
ISSN 0021-9738
1558-8238
Summary 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.
Language eng
Field of Research 060405 Gene Expression (incl Microarray and other genome-wide approaches)
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2004, American Society for Clinical Investigation
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006480

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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