Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction

Lindsay E. Wu, Christopher C. Meoli, Salvatore P. Mangiafico, Daniel J. Fazakerley, Victoria C. Cogger, Mashani Mohamad, Himani Pant, Myung Jin Kang, Elizabeth Powter, James G. Burchfield, Chrysovalantou E. Xirouchaki, A. Stefanie Mikolaizak, Jacqueline Stöckli, Ganesh Kolumam, Nicholas Van Bruggen, Jennifer R. Gamble, David G. Le Couteur, Gregory J. Cooney, Sofianos Andrikopoulos, David E. James

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Abstract

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.

Original languageEnglish
Pages (from-to)2656-2667
Number of pages12
JournalDiabetes
Volume63
Issue number8
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Cite this

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., Stöckli, J., Kolumam, G., Van Bruggen, N., Gamble, J. R., Le Couteur, D. G., Cooney, G. J., Andrikopoulos, S., & James, D. E. (2014). Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction. Diabetes, 63(8), 2656-2667. https://doi.org/10.2337/db13-1665