High- and moderate-intensity exercise training differentially impact microvascular function in skeletal muscle of mice lacking adiponectin.

We tested the hypothesis that the absence of circulating adiponectin, associated with reduced aerobic exercise, contributes to impaired microvascular function and oxidative capacity in the skeletal muscle of adult mice. Adiponectin knockout (AdipoKO) and wild-type (WT) mice were assigned to either a moderate- or high-intensity exercise (EX) training protocol or remained sedentary (SED) for an 8- to 10-wk period. At the end of this period, in vivo microvascular dynamics were measured, followed by ex vivo assessment of arteriolar vasoreactivity. Oxidative capacity and capillary density in skeletal muscle were evaluated using citrate synthase activity assays and immunohistochemical staining for lectin, respectively. Our results showed that moderate-intensity exercise training increased oxidative capacity in the soleus muscle of WT mice, whereas AdipoKO mice did not show similar improvements. Moderate-intensity exercise training also increased capillary-to-fiber ratio in WT mice; however, these exercise training-associated vascular adaptations were absent in AdipoKO mice. Moderate-intensity exercise training increased vasorelaxation to acetylcholine in arterioles from AdipoKO mice as compared with those from WT mice. In contrast, high-intensity exercise training augmented flow-mediated vasodilation in arterioles from WT mice, but not in arterioles from AdipoKO mice. These findings suggest that adiponectin is important for exercise training-induced improvements in skeletal muscle oxidative capacity and microvascular function. The lack of adiponectin disrupts these beneficial adaptations, suggesting that adiponectin plays an important role in mediating vascular health responses to aerobic exercise training in skeletal muscle.NEW & NOTEWORTHY Endothelial and microvascular adaptations to exercise are limited in the absence of adiponectin. In wild-type mice, moderate exercise improved oxidative capacity, perfusion, and capillarity, whereas high-intensity exercise enhanced flow-mediated vasodilation. These adaptations were lost in adiponectin-deficient mice, underscoring adiponectin's essential role in linking aerobic training to cardiovascular health.