Oxygen Consumption of Brown Adipose Tissue (BAT) and Skeletal Muscle is Inversely Related

Abstract

During exercise, the muscles' energy demand increases with increasing work load. In humans, the relationship between work load and oxygen uptake is linear until the maximal oxygen uptake (VO2max) is reached and higher exercise intensity requires additional anaerobic energy supply. VO2max is thought to reflect the maximum oxygen transport capacity of the cardiovascular system.We show that at room temperature normal mice could triple running speed at 25% inclination after reaching VO2max in spite of very modest increase of anaerobic muscle metabolism. In mice with cardiac dysfunction due to cardiac disruption of the Serca2 gene (S2KO), VO2max was reduced from week4 to week6 after gene disruption in parallel with progression of cardiac dysfunction. However, S2KO mice maintained maximal running speed at the same the level as the controls. Thus, paradoxically, running economy was better in S2KO than in controls. In S2KO, blood lactate was almost double of that of controls and respiratory exchange ratio was near 1, indicating greater reliance on anaerobic metabolism. However, heat production was lower in S2KO than in controls as reflected by tail temperature. Activity of BAT measured by fluoro-deoxyglucose using PET was reduced by 60±7% during running in controls and by 82±3% in running S2KO mice.In mice, the oxidative metabolism in non-muscle tissue, mainly in BAT, is reduced during exercise to provide more oxygen to the working muscles. This redistribution of oxygen delivery leaves the total VO2 unchanged over a wide range of exercise intensities. When cardiac output and VO2max are abnormally low, exercise intensity can be maintained since muscles can utilize the oxygen normally used by non-muscle tissue such as BAT. We conclude that oxygen consumption of skeletal muscle and BAT is regulated in a reciprocal way.