Author(s): TAYLOR, D., REISMAN, E., GARNHAM, A., HOFFMAN, N., HAWLEY, J., CARUANA, N., BISHOP, D.J., Institution: VICTORIA UNIVERSITY, Country: AUSTRALIA, Abstract-ID: 757

INTRODUCTION:
Exercise stimulates numerous adaptations in skeletal muscle, including increased mitochondrial content. The currently accepted dogma proposes that transient changes in the mRNA of mitochondrial genes after a single session of exercise are a major determinant of subsequent adaptations to training. However, the use of only 1 or 2 time-points post exercise, small sample sizes, and a lack of consideration for the effect of sex, has left major gaps in our understanding of exercise-induced mitochondrial gene expression.
METHODS:
RNA sequencing was performed on muscle biopsies collected before, during, and 0, 3, 6, 9, 12, 24, and 48 hours following a single session of high-intensity interval exercise from 20 healthy untrained men (27.3 ± 6.3 y; 179.6 ± 10.2 cm; 81.5 ± 12.5 kg) and 20 healthy untrained women (27.6 ± 5.6 y; 166.5 ± 7.8 cm; 68.0 ± 9.9 kg). The exercise session consisted of 4 x 4-min intervals at an intensity between each participant’s lactate threshold (LT) and peak power output (PPO), interspersed with 2 min of recovery.
RESULTS:
Our adoption of the most extensive post-exercise biopsy time course to date allowed us to identify more than 10,000 genes never previously reported to be differentially expressed by aerobic exercise; the vast majority were identified 9 to 48 hours post-exercise. Of these, 1016 were mitochondrial genes, with over 800 not previously reported to be altered by aerobic exercise. Soft clustering of the 1,016 mitochondrial differentially expressed genes revealed six characteristic patterns of expression, including clusters of early (3-6 h), mid (9-12 h), and late (24-48 h) responding genes. We also identified 675 mitochondrial genes that were downregulated 24-48 h post exercise, including most oxidative phosphorylation complex subunits. Transcription factor enrichment analysis using an aggregated ChIP-Seq dataset library identified the MYC transcription factor network as a key regulator for many of these gene clusters. Similarly, p53 was identified as an important regulator of late-responding genes. Although there were over 500 genes detected as differentially expressed between men and women at baseline, sex had a minimal effect on the expression of mitochondrial genes in response to exercise.
CONCLUSION:
Our unique study was able to produce the most extensive description to date of the exercise-induced transcriptome, with over 14,000 genes identified as differentially expressed. Interestingly, several diverging patterns of expression for mitochondrial genes were found, indicating regulation by various transcriptional factor networks and potentially a high degree of variance in post-transcriptional regulation. By obtaining a statistical power above 0.85, and use of an exercise intensity based on both LT and PPO, we were able to detect fewer sex differences for exercise-induced mitochondrial gene expression than previously assumed.