Aging differentially impacts vasodilation and angiogenesis in arteries from the white and brown adipose tissues

Aging adipose tissues (ATs) manifest reduced vascularity and increased hypoxia and inflammation that contribute to local and systemic metabolic dysfunction. However, the mechanisms that underlie these age-related changes are incompletely understood. In this study, we sought to examine insulin-stimulated vasodilation and angiogenesis in the arterial vasculature from three major AT depots, perigonadal white (pgWAT), subcutaneous white (scWAT) and brown (BAT) from young and old mice. Here, we demonstrate that in young mice, insulin-stimulated vasodilation is lower in feed arteries from pgWAT compared to scWAT (p < 0.05), but no differences were found between feed arteries in other AT depots (p > 0.05). Insulin-stimulated vasodilation was lower in old compared to young feed arteries from all three AT depots (p < 0.05 for all). In the presence of endothelial nitric oxide synthase inhibitor, L-NAME, insulin-stimulated vasodilation was decreased in young (p < 0.05), but was unaffected in old (p > 0.05) from all AT depots. We also observed no age-related differences in endothelium-independent dilation, as assessed by sodium nitroprusside (p > 0.05). We next investigated angiogenic capacity of the vasculature in these AT depots. In young mice, BAT vasculature demonstrated the highest angiogenic potential, followed by pgWAT and scWAT. We found that aging decreased angiogenic sprout formation in pgWAT and BAT (both p < 0.05), but increased angiogenic potential in scWAT (p < 0.05), indicating dissimilar impact of aging on angiogenesis in different AT depots. Collectively, these data suggest that aging leads to a consistent impairment in insulin-stimulated vasodilation and reduction in NO bioavailability in all three AT, although aging differentially impacts angiogenic capacity across different AT depots.