Referenced in: none

Automatically associated channels: Kv10.1

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

Authors: Juan C Molero, Thomas E Jensen, Phil C Withers, Michelle Couzens, Herbert Herzog, Christine B F Thien, Wallace Y Langdon, Ken Walder, Maria A Murphy, David D L Bowtell, David E James, Gregory J Cooney

Journal, date & volume: J. Clin. Invest., 2004 Nov , 114, 1326-33

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15520865

Abstract
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.