The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the present study, we sought to identify the effects of vascular endothelial growth factor A (VEGF-A) neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high fat diet induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole body adiposity or insulin signalling. These findings show an important and unexpected role for VEGF in liver insulin resistance opening up a potentially novel therapeutic avenue for obesity related metabolic disease.
* These authors contributed equally to this work.
- Received October 28, 2013.
- Accepted March 25, 2014.
- © 2014 by the American Diabetes Association.
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