Short-duration intermittent hypoxia enhances endurance capacity by improving muscle fatty acid metabolism in mice.

This study was designed to (1) investigate the effects of acute short-duration intermittent hypoxia on musclemRNAand microRNAexpression levels; and (2) clarify the mechanisms by which short-duration intermittent hypoxia improves endurance capacity. Experiment-1: Male mice were subjected to either acute 1-h hypoxia (12% O2), acute short-duration intermittent hypoxia (12% O2for 15 min, room air for 10 min, 4 times, Int-Hypo), or acute endurance exercise (Ex). The expression of vascular endothelial growth factor-AmRNAwas significantly greater than the control at 0 h post Ex and 6 h post Int-Hypo in the deep red region of the gastrocnemius muscle. miR-16 expression levels were significantly lower at 6 and 10 h post Int-Hypo. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)mRNAlevels were significantly greater than the control at 3 h post Ex and 6 h post Int-Hypo. miR-23a expression levels were lower than the control at 6-24 h post Int-Hypo. Experiment-2: Mice were subjected to normoxic exercise training with or without intermittent hypoxia for 3 weeks. Increases in maximal exercise capacity were significantly greater by training with short-duration intermittent hypoxia (IntTr) than without hypoxia. Both 3-Hydroxyacyl-CoA-dehydrogenase and total carnitine palmitoyl transferase activities were significantly enhanced in IntTr. Peroxisome proliferator-activated receptor delta andPGC-1α mRNAlevels were both significantly greater in IntTr than in the sedentary controls. These results suggest that exercise training under normoxic conditions with exposure to short-duration intermittent hypoxia represents a beneficial strategy for increasing endurance performance by enhancing fatty acid metabolism in skeletal muscle.