C-Cbl-deficient Mice Have Reduced Adiposity, Higher Energy Expenditure, and Improved Peripheral Insulin Action

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2004 Nov 3

PMID 15520865

Citations 48

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

Affiliations

Soon will be listed here.

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.

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