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Published on: February 13, 2019
Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
Lindsay E Wu1, Christopher C Meoli2, Salvatore P Mangiafico3
1Diabetes 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.
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.
Insights
Neutralizing vascular endothelial growth factor (VEGF) rapidly reversed obesity-induced insulin resistance in mice. This suggests VEGF plays a key role in metabolic dysfunction, offering a new therapeutic target for obesity.
Area of Science:
- Endocrinology
- Metabolic disease research
- Angiogenesis and metabolic regulation
Background:
- Vascular endothelial growth factor (VEGF) is crucial for angiogenesis and implicated in obesity.
- Conflicting evidence exists regarding VEGF's role in obesity-related metabolic dysfunction.
- Understanding VEGF's precise impact is vital for developing effective obesity treatments.
Purpose of the Study:
- To investigate the effect of VEGF-A neutralization on glucose metabolism and insulin action in a diet-induced obesity mouse model.
- To determine if blocking VEGF-A can ameliorate insulin resistance associated with obesity.
Main Methods:
- Utilized a mouse model of diet-induced obesity.
- Administered a VEGF-A-neutralizing monoclonal antibody (B.20-4.1).
- Assessed parameters of glucose metabolism and insulin sensitivity within 72 hours.
Main Results:
- Rapid reversal of high-fat diet-induced insulin resistance observed within 72 hours.
- Improved insulin sensitivity in liver and adipose tissue was the primary driver of this reversal.
- These metabolic improvements occurred independently of changes in overall body fat or insulin signaling pathways.
Conclusions:
- VEGF-A neutralization rapidly improves insulin sensitivity and reverses obesity-induced insulin resistance.
- VEGF plays a significant, previously unrecognized role in hepatic insulin resistance.
- Targeting VEGF presents a novel therapeutic strategy for metabolic diseases associated with obesity.
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