New insights into adipose tissue VEGF-A actions in the control of obesity and insulin resistance

Abstract

Vascular endothelial growth factor A (VEGF-A) is classically viewed as a key factor in angiogenesis and tissue remodeling. However, recent evidence suggests a potential role of this growth factor in the control of energy metabolism and adipose tissue function. In this regard, we and others have described the effects of the up and downregulation of VEGF-A in adipose tissue on the control of energy homeostasis. VEGF-A overexpression protects against diet-induced obesity and insulin resistance. The observation that VEGF-A overexpression leads to an increase in brown adipose tissue (BAT) thermogenesis and also promotes a "BAT-like" phenotype in white adipose tissue depots is of particular relevance for the understanding of the mechanisms underlying obesity development. In addition, VEGF-A may not only have pro-inflammatory but also anti-inflammatory properties, with a chemotactic activity specific for M2 anti-inflammatory macrophages. This new scientific evidence highlights the importance that VEGF-A actions on metabolism could have on the design of new treatments for obesity, insulin resistance and obesity-related disorders.

Keywords: VEGF-A; adipose tissue; inflammation; insulin resistance; obesity.

Figure 1. Schematic representation of the impact of VEGF-A overexpression in adipose tissue on insulin resistance. VEGF-A overexpression promotes a “BAT-like” phenotype in WAT depots and enhances PGC-1α and UCP-1 expression in BAT, leading to increased thermogenesis and energy expenditure and reduced obesity. VEGF-A overexpression also exerts its action on macrophages by increasing the recruitment of M2 anti-inflammatory macrophages to fat depots. The decreased obesity and the anti-inflammatory milieu induced by VEGF-A in adipose tissue may be responsible for the reduction of insulin resistance in transgenic mice.