Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity

Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1(fl/fl)) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1(fl/fl) mice show remarkable muscle atrophy compared to Hmox1(fl/fl) controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

Automated summary

This study reveals the central role of heme and HO-1 in regulating the physiological response of skeletal muscle to exercise, highlighting the importance of effective heme metabolism in maintaining muscle function. The experiment demonstrates that control over HO-1 is crucial in maintaining the normal function of muscles in the presence of microtraumatic events leading to accumulation of circulating heme.