Metabolic stress-dependent regulation of the mitochondrial biogenic molecular response to high-intensity exercise in human skeletal muscle.
Level 2 - randomized trial
Randomized crossover trial evaluating acute physiological and molecular responses
PubMed 29727016 · doi:10.1113/JP275972
What was done
Twelve endurance-trained men performed three cycling protocols in a randomized, counter-balanced crossover design: two work-matched low-volume supramaximal intermittent regimens—repeated-sprint (RS) and speed endurance (SE)—and one high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle biopsies and blood samples were collected before, immediately after, and 3 hours post-exercise to assess muscle lactate, pH, plasma adrenaline, protein phosphorylation (CaMKII, p38 MAPK), and transcriptional responses of mitochondrial biogenesis- and stress-related genes (PGC-1α, NRF-2, TFAM, MFN2, DRP1, SOD2, HSP72).
What was found
SE induced the largest metabolic disturbance, showing the greatest shifts in muscle lactate and pH along with higher post-exercise plasma adrenaline than RS and CM. Phosphorylation of CaMKII and p38 MAPK was greater following SE than RS and CM. PGC-1α mRNA expression was elevated to an equivalent degree in SE and CM, with both greater than RS. Muscle mRNA levels for NRF-2, TFAM, MFN2, DRP1, and SOD2 were equally increased by SE and CM, whereas RS had no effect. HSP72 mRNA was higher after SE than after RS or CM. Specific numerical values and effect sizes were not reported in the abstract.
Why it matters
These findings indicate that metabolic stress is an essential trigger for acute mitochondrial biogenic signaling in skeletal muscle. This explains mechanistically how low-volume, high-intensity exercise can match the molecular adaptations typically achieved only with high-volume moderate-intensity training.
Limits
The study is limited by a small sample size (n = 12) restricted exclusively to endurance-trained men, limiting direct generalizability to women, untrained individuals, or clinical populations. It evaluated only acute molecular and transcriptional responses up to 3 hours post-exercise rather than long-term mitochondrial adaptations or clinical functional outcomes.
Cited by
- supports Both high-intensity interval training and Zone 2 moderate-intensity training increase mitochondrial biogenesis in skeletal muscle, with HIIT stimulating it more rapidly.