Exercise performance in well-trained male mice is promoted by intermittent hyperoxia via improving metabolic properties and capillary profiles.

Although training under intermittent hyperoxia has been shown to improve exercise performance, its effect on well-trained mice remains undetermined. Voluntary run for 7 weeks increased maximal work values by 7.4-fold (Bayes factor, BF ≥ 30). Subsequently, mice underwent 4 weeks of treadmill training with (INT) or without (ET) intermittent hyperoxia (30% O₂). INT training significantly increased maximal exercise capacity compared to ET (BF ≥ 30). INT group exhibited significantly higher levels of cytochrome-c-oxidase (COX) in soleus muscle (SOL, BF ≥ 3.0). Additionally, INT enhanced 3-hydroxyacyl-CoA-dehydrogenase (HAD) levels in white gastrocnemius (Gw) and plantaris (PL) muscles compared to ET (BF ≥ 3.0). Pyruvate dehydrogenase complex (PDHc) levels were significantly higher in the INT group compared to the ET group in red gastrocnemius and left ventricle (BF ≥ 30). Capillary-to-fiber ratio (C/F) was significantly higher in the INT group than in the ET group in SOL and PL muscles (BF ≥ 3.0). COX, PDHc, capillary density (CD), and catalase protein values in SOL, HAD, and C/F levels in Gw and PL, as well as CD values in Gw showed a significant positive correlation with maximal work values using data from ET and INT groups (p < 0.05). These findings suggest that training under intermittent hyperoxia promotes endurance performance probably by improving metabolic enzyme levels and capillary profiles in well-trained mice.