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 muscle mRNA and microRNA expression 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% O(2)), acute short‐duration intermittent hypoxia (12% O(2) for 15 min, room air for 10 min, 4 times, Int‐Hypo), or acute endurance exercise (Ex). The expression of vascular endothelial growth factor‐A mRNA was 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) mRNA levels 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 and PGC‐1α mRNA levels 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.