Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb−/− mice

Abstract Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO • bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake () and exercise performance in myoglobin knockout mice ( Mb −/− ) when compared to control mice ( Mb +/+ ). Furthermore, we also studied NO • bioavailability, assessed as nitrite (NO 2 − ) and nitrate (NO 3 − ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb −/− and in Mb +/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole‐body gas exchange measurements. The Mb −/− mice had lower body mass, heart and hind limb muscle mass ( P < 0.001). Mb −/− mice had significantly reduced maximal running performance ( P < 0.001). expressed in ml min −1 in Mb −/ − mice was 37% lower than in Mb +/+ mice ( P < 0.001) and 13% lower when expressed in ml min −1 kg body mass −1 ( P = 0.001). Additionally, Mb −/− mice had significantly lower plasma, heart and locomotory muscle NO 2 − levels at rest. During exercise NO 2 − increased significantly in the heart and locomotory muscles of Mb −/− and Mb +/+ mice, whereas no significant changes in NO 2 − were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs and maximal running performance in mice. image Key points Myoglobin knockout mice ( Mb −/− ) possess lower maximal oxygen uptake () and poorer maximal running performance than control mice ( Mb +/+ ). Respiratory exchange ratio values at high running velocities in Mb −/− mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb −/− mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO • bioavailability, but does not affect exercise‐induced NO 2 − changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb −/− mouse model.