Dichotomous effects of VEGF-A on adipose tissue dysfunction

• DOI: 10.1073/pnas.1200447109
• Publication Date: 2012-03-27T04:28:13Z
• Authors: Kai Sun; Ingrid Wernstedt ...; Christine M. Kusm...; Ana Carolina Bueno; Zhao V. Wang; Jeffrey W. Pollard; Rolf A. Brekken; Philipp E. Scherer
• Keywords: Proinflammatory cytokine; Adipose tissue macrophages

Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained sufficient oxygen nutrient exchange during mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate the local up-regulation in adipocytes improves vascularization causes "browning" white (AT), with massive UCP1 PGC1α. This is associated an increase energy expenditure resistance high diet-mediated metabolic insults. Similarly, inhibition activation VEGFR2 early phase diet-induced weight gain, aggravated systemic However, same VEGF-A-VEGFR2 blockade ob/ob mice leads reduced body-weight improvement sensitivity, decrease inflammatory factors, incidence adipocyte death. The consequences modulation angiogenic activity therefore context dependent. Proangiogenic expansion beneficial, potent protective effects on metabolism, whereas antiangiogenic action preexisting dysfunction improvements effect likely mediated by ablation dysfunctional proinflammatory adipocytes.