Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Introduction: Obesity (OB) impairs cell-to-cell communication signaling. Small extracellular vesicles (EVs), which includes exosomes, are released by skeletal muscle and participate in cell-to-cell communications including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fiber size and capillarization. However, while obesity increases muscle fiber size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx induced angiogenic signaling and EV biogenesis would be lower with obesity.

Methods: Sedentary lean (LN) and individuals with obesity (OB) (n = 8/group) performed three sets of single leg, knee extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min, and 3 hr post-exercise and analyzed for angiogenic and EV biogenesis mRNA and protein.

Results: In OB, muscle fiber size was ∼20% greater and capillary density with type II fibers was ∼25% lower compared to LN (p<0.001) . In response to REx, increased vascular endothelial growth factor (VEGF) mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased ∼2.5-fold in OB only (p = 0.010). miR-130a (pro-angiogenic) was ∼1.4-fold (p = 0.011) and miR-503 (anti-angiogenic) was ∼1.8-fold (p = 0.017) greater in OB compared to LN across all time points. In both groups acute REx decreased the EV surface protein Alix ∼50% consistent with the release of exosomes (p = 0.016).

Conclusion: Acute resistance exercise appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signaling consistent with inadequate angiogenesis in response to basal muscle hypertrophy.