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Systemic VEGF-A Neutralization Ameliorates Diet-Induced Metabolic Dysfunction


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 current study, we sought to identify the effects of 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 signaling. 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.

Type Journal
ISBN 1939-327X (Electronic) 0012-1797 (Linking)
Authors Wu, L. E. ; Meoli, C. C. ; Mangiafico, S. P. ; Fazakerley, D. J. ; Cogger, V. C. ; Mohamad, M. ; Pant, H. ; Kang, M. J. ; Powter, E. ; Burchfield, J. G. ; Xirouchaki, C. E. ; Mikolaizak, A. S. ; Stockli, J. ; Kolumam, G. ; van Bruggen, N. ; Gamble, J. R. ; Le Couteur, D. G. ; Cooney, G. J. ; Andrikopoulos, S. ; James, D. E.;
Publisher Name DIABETES
Published Date 2014-01-01
Published Volume 63
Published Issue 8
Published Pages 2656-67
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version