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Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction

Wu LE 1 , Meoli CC 2 , Mangiafico SP 3 , Fazakerley DJ 2 , Cogger VC 4 , Mohamad M 5 Show all authors , Pant H 2 , Kang MJ 6 , Powter E 7 , Burchfield JG 2 , Xirouchaki CE 3 , Mikolaizak AS 8 , Stöckli J 2 , Kolumam G 9 , van Bruggen N 9 , Gamble JR 7 , Le Couteur DG 4 , Cooney GJ 2 , Andrikopoulos S 3 , James DE 10

Affiliations 

  • 1 Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, AustraliaLaboratory for Ageing Research, School of Medical Sciences, UNSW Australia, New South Wales, Australia
  • 2 Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
  • 3 Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia
  • 4 Centre for Education and Research on Ageing and ANZAC Medical Research Institute, University of Sydney and Concord Hospital, Concord, New South Wales, Australia
  • 5 Centre for Education and Research on Ageing and ANZAC Medical Research Institute, University of Sydney and Concord Hospital, Concord, New South Wales, AustraliaFaculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam, Selangor, Malaysia
  • 6 Laboratory for Ageing Research, School of Medical Sciences, UNSW Australia, New South Wales, Australia
  • 7 Centre for the Endothelium, Vascular Biology Program, Centenary Institute, and The University of Sydney, Sydney, Australia
  • 8 Falls and Balance Research Group, Neuroscience Research Australia, Sydney, Australia
  • 9 Department of Biomedical Imaging, Genentech Inc., San Francisco, CA
  • 10 Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, AustraliaCharles Perkins Centre, School of Molecular Bioscience, The University of Sydney, Sydney, Australia david.james@sydney.edu.au
Diabetes, 2014 Aug;63(8):2656-67.
PMID: 24696450 DOI: 10.2337/db13-1665

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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