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Published on: February 13, 2019
Dichotomous effects of VEGF-A on adipose tissue dysfunction
Kai Sun1, Ingrid Wernstedt Asterholm, Christine M Kusminski
1Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Summary
Vascular Endothelial Growth Factor-A (VEGF-A) promotes beneficial blood vessel growth in expanding fat tissue, improving metabolism. However, blocking VEGF-A in dysfunctional fat can improve metabolic health by clearing inflamed cells.
Area of Science:
- Metabolic disease
- Adipose tissue biology
- Angiogenesis
Background:
- Obesity leads to undervascularized and hypoxic adipose tissue, promoting fibrosis, inflammation, and insulin resistance.
- Adipose tissue dysfunction is a key driver of metabolic complications associated with obesity.
Purpose of the Study:
- To investigate the role of Vascular Endothelial Growth Factor-A (VEGF-A) in regulating adipose tissue vascularization and function.
- To determine the impact of modulating VEGF-A signaling on metabolic health in different obesity contexts.
Main Methods:
- Utilized a doxycycline-inducible, adipocyte-specific VEGF-A overexpression mouse model.
- Administered VEGF-A/VEGFR2 blockade in diet-induced obesity and genetic obesity (ob/ob) mouse models.
- Assessed adipose tissue vascularization, "browning" markers (UCP1, PGC1α), energy expenditure, insulin sensitivity, and inflammatory factors.
Main Results:
- Adipocyte-specific VEGF-A overexpression improved vascularization, induced adipose tissue "browning," increased energy expenditure, and conferred resistance to high-fat diet-induced metabolic dysfunction.
- Early VEGF-A/VEGFR2 blockade during high-fat diet-induced weight gain aggravated insulin resistance.
- VEGF-A/VEGFR2 blockade in ob/ob mice reduced body weight, improved insulin sensitivity, decreased inflammation, and increased adipocyte death.
Conclusions:
- Proangiogenic activity driven by VEGF-A is beneficial during adipose tissue expansion, protecting against metabolic insults.
- Antiangiogenic strategies targeting VEGF-A/VEGFR2 in established adipose tissue dysfunction can improve metabolic parameters, potentially via eliminating dysfunctional adipocytes.
