Metabolic stress-dependent regulation of the mitochondrial biogenic molecular response to high-intensity exercise in human skeletal muscle

The aim of the present study was to examine the impact of exercise-induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance-trained men performed three cycling-exercise protocols characterized by different metabolic profiles in a randomized, counter-balanced order. Specifically, two work-matched low-volume supramaximal-intensity intermittent regimes, consisting of repeated-sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post-exercise plasma adrenaline levels in comparison with RS and CM (P < 0.05). Exercise-induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise-induced PGC-1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF-2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise-induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high-intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.