0259 : Physical exercise induced adipose tissue angio-adaptation in a context of “diabesity”

Abstract

Adipose tissue (AT) homeostasis and growth are dependent on microvasculature. This capillary network has a large remodeling capacity, a process called angio-adaptation. In response to metabolic alterations linked to obesity, signaling pathways involved in the maintenance of vascular homeostasis of AT appear to be affected. In this context, we studied in C57/Bl6 subject to an high fat diet (HFD) and voluntary exercise protocol of 7weeks, capillarisation of epididymal (eWAT) and subcutaneous adipose tissue (sWAT) by histological marking of CD31, and expression of angiogenic factors: Murinedouble- minute 2 (MDM-2), vascular endothelial growth factor (VEGF-A) and trombospondin (TSP-1). Morphometric analysis of mice showed a significant reduction of 30% in the ratio of AT/total mass in HFD trained mice at 7weeks of exercise. In these mice, % of mass eWAT/total and sWAT/total significantly reduced by 33 and 39%, respectively, which was associated to a significant decrease in adipocytes size by 26% in eWAT and 30% in sWAT of HFD mice at 7weeks of exercise. Biochemical study showed that exercise led to an increase of MDM-2 expression and VEGF-A/TSP-1 ratio and in AT of control and HFD mice after 7weeks of exercise pointing the emerging of a angio-adaptive response in favor of capillary growth in AT, was was confirmed by a significant increase of the capillary density (capillaries/mm 2 ) in AT of control mice (55 and 36% respectively in eWAT and sWAT) and a capillaries/adipocyte ratio significantly increased in HFD trained mice (respectively 16 and 18% in eWAT and sWAT). These results showed for the first time that physical exercise acts as a pro-angiogenic stimulus in AT in favor of capillary growth, thru activation of MDM-2, and VEGF-A/TSP-1 ratio