The impact of acute and chronic exercise on Nrf2 expression in relation to markers of mitochondrial biogenesis in human skeletal muscle.
Level 4 - case-series / case-control
Pre-post physiological intervention without a non-exercising control group.
PubMed 31707475 · doi:10.1007/s00421-019-04259-7
What was done
Ten healthy young men underwent acute submaximal endurance and supramaximal interval (Tabata) cycling to evaluate skeletal muscle mRNA expression of Nrf2, NRF-1, TFAM, and downstream antioxidant targets. In a separate cohort of 21 healthy males, skeletal muscle citrate synthase (CS) activity and protein levels of Nrf2, HO-1, NRF-1, and TFAM were measured before and after 4 weeks of Tabata interval training. Participants were also stratified into high (HI: +23%, n = 8) and low (LO: -1%, n = 8) responders based on changes in CS activity.
What was found
Acute exercise significantly increased skeletal muscle mRNA expression of Nrf2, NRF-1, and HO-1 (p < 0.05), while SOD2 mRNA changes trended toward significance (p = 0.08). Four weeks of Tabata training significantly increased CS maximal activity as well as Nrf2, NRF-1, and TFAM protein content (p < 0.05), whereas HO-1 protein content significantly decreased (p < 0.05). Training-induced changes in Nrf2 protein correlated positively with NRF-1 protein changes (r = 0.63, p < 0.01). Significant increases in Nrf2 and TFAM protein were observed exclusively in the high-responder group (p < 0.02; partial η² = 0.15 for Nrf2 and 0.12 for TFAM).
Why it matters
These findings demonstrate in human skeletal muscle that Nrf2 responds to both acute and chronic high-intensity exercise and tracks closely with mitochondrial biogenesis adaptations, supporting a potential regulatory role for Nrf2 in exercise-induced mitochondrial remodeling.
Limits
The study was conducted exclusively in small cohorts of healthy young males (n = 10 and n = 21), limiting generalizability to females, older adults, or clinical populations. There was no non-exercising control group to account for time or repeated testing effects, and the correlational design cannot establish whether Nrf2 is mechanistically required for mitochondrial biogenesis. Absolute baseline values, standard deviations, and exact p-values were omitted for several endpoints in the abstract.
Cited by
- supports In young people, exercise increases NRF2 expression, whereas in people over 60, over-exercising causes NRF2 levels to decline.