0230 : Physical exercise angio-adaptation ameliorates metabolic dysfunction and inflammation in visceral adipose tissue of diet-induced obese mice

Adipose tissue (AT) homeostasis and growth are dependent on microvasculature. Adipose capillary bed displays a remarkable plasticity, a process called tissue angio-adaptation. In response to metabolic alterations linked to obesity, signaling pathways involved in vascular and microenvironment homeostasis maintenance of AT appear to be affected. We demonstrated that Mdm-2/FoxO1 axis had a key role in muscle angio-adaptive response to exercise affecting pro- (VEGF-A) and anti-angiogenic (TSP-1) factors expression. However, regulation of this process in AT occurring during obesity and/or physical exercise remains unknown. In this context, we studied effects of voluntary exercise in mice fed with a high fat diet (HFD) on the AT vascularization and microenvironment. Trained HFD mice after 7 week-exercise showed a 30% lower body fat mass and 33% reduced epididymal white adipose tissue (eWAT) mass compared to sedentary HFD mice. Histological analysis of eWAT revealed a decreased adipocyte size (-26%) combined with reduced fibrotic area per adipocyte (-45%) in trained HFD vs. sedentary HFD mice. Furthermore, 7 weeks of exercise training of HFD mice stimulated the angiogenesis process in AT with significant increased of capillaries/adipocyte ratio on eWAT (+16%) associated to VEGF-A/TSP-1 expression ratio and Mdm 2 protein expression while FoxO1 protein was decreased. In addition, eWAT inflammatory status evaluated by mRNA analysis indicated that CD11c (M1 macrophage marker), TNFα, IL-6 and leptin (pro-inflammatory cytokines) levels were decreased by 65%, 45% and 55% respectively in comparison to eWAT from sedentary HFD mice. A concomitant increase in Chil3 (M2 macrophage marker) (+84%) and IL-10 (anti-inflammatory cytokine) (+29%) were also observed. In conclusion, our results show that physical exercise acts as a pro-angiogenic stimulus in AT in favor of capillary growth, thru activation of Mdm 2 – FoxO1 and rise of VEGF-A/TSP-1 ratio ultimately promoting an improvement of AT microenvironment by reducing fibrosis, adipocyte hypertrophy and inflammation. The author hereby declares no conflict of interest