0311 : Physical exercise regulates angiogenesis in adipose tissue of dietinduced obese mice thru ECSCR/Akt pathways

Abstract

Reduced capillary density in adipose tissue is associated with obesity and results in decrease perfusion, decreased oxygen consumption and insulin resistance. Pro- (VEGF-A) and anti-angiogenic (TSP-1) factors expression is central determinant of angiogenesis, with greater VEGF-A/TSP-1 ratio promoting angiogenesis. Since endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis, we investigated the role of ECSCR (endothelial cell surface expressed chemotaxis and apoptosis regulator) – Akt axis. In this context, we studied effects of voluntary exercise in mice fed with a high fat diet (HFD) on the AT vascularization. We have demonstrated that 7 weeks-exercise training reduced epididymal and subcutaneous white adipose tissue (eWAT) and (sWAT) mass by 33% and 45% respectively compared to sedentary HFD mice and stimulated capillary growth in AT with a significant increased of capillaries/ adipocyte ratio on eWAT and sWAT (+16% and 28% respectively), associated with a significant VEGF-A/TSP-1 expression ratio increase. Furthermore, while ECSCR protein expression was decreased and associated to a lower ratio of PhosphoAkt/Akt in eWAT and sWAT of HFD mice in comparison to control mice, 7 weeks-exercise training led to a significant increase of ECSCR protein expression associated to the raise of PhosphoAkt/Akt ratio in both eWAT and sWAT. In addition, eWAT and sWAT thermogenic and metabolic activities were stimulated by 7 weeks-exercise training, with increased PGC-1α, Sirt-3 and PPARα in comparison to eWAT and sWAT from sedentary HFD mice. In conclusion, our results indicate that physical exercise acts as a pro-angiogenic stimulus in AT in favor of capillary growth, and that ECSCR – Akt axis as well as VEGF-A/TSP-1 play central role in angioadaptation of AT. The author hereby declares no conflict of interest