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c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action

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journal contribution
posted on 2004-11-01, 00:00 authored by Juan Molero Navajas, T Jensen, P Withers, M Couzens, H Herzog, C Thien, W Langdon, Ken WalderKen Walder, M Murphy, D Bowtell, D James, G Cooney
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.

History

Journal

Journal of clinical investigation

Volume

114

Pagination

1326 - 1333

Location

New York, N.Y.

Open access

  • Yes

ISSN

0021-9738

eISSN

1558-8238

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2004, American Society for Clinical Investigation