Higher Workload, not Hypoxia, Enhances Acute Mitochondrial Respiratory Responses to High-Intensity Interval Exercise...

This study investigated whether skeletal muscle mitochondrial responses to a single session of high-intensity interval exercise (HIIE) in men with overweight or obesity were influenced by hypoxia or absolute power output. The HIIE performed in hypoxia (HY; inspired oxygen fraction [FiO2] = 14.0%) was matched with HIIE performed in normoxia (FiO₂ = 20.9%) for either absolute power output (NA) or relative intensity (NR). Our primary hypothesis was that both HY and NR would elicit greater acute increases in skeletal muscle mitochondrial respiratory capacity than NA. Our secondary hypothesis was that HY and NR would produce comparable skeletal muscle oxygen desaturation and responses in mitochondrial-related gene expression and protein content.

Twelve men with overweight or obesity (mean±standard deviation [SD]: age, 32.3±7.3 years; body mass index [BMI], 29.0±1.9 kg·m⁻²) completed HIIE under three experimental conditions (HY, NR, and NA) in a randomized crossover design, with each trial separated by a one-week washout period. Exercise intensities were prescribed using lactate threshold (LT) and peak power output (PPO) obtained during graded exercise tests (GXT). HY and NA were matched for absolute power output (185±57 W) using the LT and PPO obtained from the hypoxic GXTs. NR was matched to HY for relative intensity using the LT and PPO obtained from the normoxic GXTs, resulting in a higher power output (210±65 W) than in HY and NA. Each HIIE consisted of six 4-min cycling intervals interspersed with 2-min recovery periods. Venous blood samples and vastus lateralis muscle biopsies were obtained at baseline and 0, 3, and 24 h post-exercise.

Arterial oxygen saturation and muscle tissue saturation index were lower during HY compared with NA (p<0.05). Twenty-four hours after HIIE, electron transfer flavoprotein- and complex I+II-linked oxidative phosphorylation and electron transport system capacities [(ETF+CI+II)P and (ETF+CI+II)E] were greater following NR than NA (p<0.05). Mitochondrial DNA copy number and citrate synthase activity were unchanged. PGC-1α and PGC-1α4 mRNA expression levels significantly increased 3 h after HIIE relative to baseline in all conditions (p<0.05), with no significant differences between conditions (p>0.05). HIF-1α and VEGF mRNA increased following NR and HY, respectively (p<0.05). Protein expression of PGC-1α and phosphorylated p38 increased immediately after NA and NR, while phosphorylated mTOR increased after NR (p<0.05). HIF-1α protein increased 3 and 24 h post-HIIE in NR (p<0.05).

Despite greater systemic and muscle oxygen desaturation, hypoxic HIIE did not enhance mitochondrial respiratory capacity or markers of mitochondrial content and biogenesis. Conversely, mitochondrial respiration increased following normoxic HIIE performed at a higher power output, suggesting that exercise workload, rather than hypoxia, may be an important determinant of the acute mitochondrial respiratory response to HIIE in men with overweight or obesity.