Casitas b-lineage lymphoma-deficient mice are protected against high-fat died-induced obesity and insulin resistance

Molero - Navajas, J, Warning, S, Cooper, A, Turner, N, Laybutt, R, Cooney, G and James, D 2006, 'Casitas b-lineage lymphoma-deficient mice are protected against high-fat died-induced obesity and insulin resistance', Diabetes, vol. 55, no. 3, pp. 708-715.


Document type: Journal Article
Collection: Journal Articles

Title Casitas b-lineage lymphoma-deficient mice are protected against high-fat died-induced obesity and insulin resistance
Author(s) Molero - Navajas, J
Warning, S
Cooper, A
Turner, N
Laybutt, R
Cooney, G
James, D
Year 2006
Journal name Diabetes
Volume number 55
Issue number 3
Start page 708
End page 715
Total pages 8
Publisher American Diabetes Association
Abstract Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity involved in regulating the degradation of receptor tyrosine kinases. We have recently reported that c-Cbl -/- mice exhibit a lean phenotype and enhanced peripheral insulin action likely due to elevated energy expenditure. In the study reported here, we examined the effect of a high-fat diet on energy homeostasis and glucose metabolism in these animals. When c-Cbl -/- mice were fed a high-fat diet for 4 weeks, they maintained hyperphagia, higher whole-body oxygen consumption (27%), and greater activity (threefold) compared with wild-type animals fed the same diet. In addition, the activity of several enzymes involved in mitochondrial fat oxidation and the phosphorylation of acetyl CoA carboxylase was significantly increased in muscle of high-fat-fed c-Cbl-deficient mice, indicating a greater capacity for fat oxidation in these animals. As a result of these differences, fat-fed c-Cbl -/- mice were 30% leaner than wild-type animals and were protected against high-fat diet-induced insulin resistance. These studies are consistent with a role for c-Cbl in regulating nutrient partitioning in skeletal muscle and emphasize the potential of c-Cbl as a therapeutic target in the treatment of obesity and type 2 diabetes.
Subject Animal Physiology - Cell
Keyword(s) acetyl coenzyme A carboxylase
Cbl protein
fat
glucose
insulin
oxygen
DOI - identifier 10.2337/diabetes.55.03.06.db05-0312
Copyright notice © 2006 by the American Diabetes Association.
ISSN 0012-1797
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