Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction

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...

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Published in:Diabetes
Main Author: 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.
Format: Article
Language:English
Published: American Diabetes Association Inc. 2014
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905046885&doi=10.2337%2fdb13-1665&partnerID=40&md5=e3d240353d2f2c6d56cfd3141950ab34
id 2-s2.0-84905046885
spelling 2-s2.0-84905046885
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.
Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
2014
Diabetes
63
8
10.2337/db13-1665
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905046885&doi=10.2337%2fdb13-1665&partnerID=40&md5=e3d240353d2f2c6d56cfd3141950ab34
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. © 2014 by the American Diabetes Association.
American Diabetes Association Inc.
121797
English
Article
author 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.
spellingShingle 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.
Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
author_facet 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.
author_sort 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.
title Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
title_short Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
title_full Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
title_fullStr Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
title_full_unstemmed Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
title_sort Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
publishDate 2014
container_title Diabetes
container_volume 63
container_issue 8
doi_str_mv 10.2337/db13-1665
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905046885&doi=10.2337%2fdb13-1665&partnerID=40&md5=e3d240353d2f2c6d56cfd3141950ab34
description 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. © 2014 by the American Diabetes Association.
publisher American Diabetes Association Inc.
issn 121797
language English
format Article
accesstype
record_format scopus
collection Scopus
_version_ 1823296165554159616

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