Exercise induces time-dependent but not sex-specific transcriptomic changes in healthy human skeletal muscle

Key results

1. ShownSampling through +48 h shows that nearly every gene quantified in vastus lateralis responds to a single interval session, including more than 7,000 genes not reported as exercise-responsive in prior studies.

   16,625 of 17,345 analysed genes (96%) were differentially expressed genes (DEGs) vs PRE (pre-exercise) at one or more time points (adjusted p < 0.05, sexes pooled), covering 81% of previously reported exercise DEGs. Participant subsampling (100 iterations) indicated the larger cohort accounted for less than 15% of newly identified genes. · An emphasis on early post-exercise time points…; Statistical analysis; Figure legends

2. ShownExpression changes keep accumulating for a day after exercise, downregulation outweighs upregulation from +3 h onward, and the apparent direction of well-studied genes such as PPARGC1A depends on when the biopsy is taken.

   Up- and downregulated DEG numbers grew at each time point until +24 h and fell slightly at +48 h; from +3 h through +48 h, downregulated genes outnumbered upregulated ones at every time point; over 4,100 genes went up at some times and down at others. NR4A3, the most upregulated gene, peaked at +3 h and returned to baseline by +48 h; PPARGC1A rose at +3 to +9 h, was not DE at +12 h, and fell at +24 and +48 h. · Exercise-induced gene expression is temporal and…

3. SuggestedLower cardiorespiratory fitness (maximal oxygen uptake, VO2max) goes with larger exercise-induced expression changes, mainly at +24 and +48 h, with ribosome biogenesis and (at +12 h) mitochondrial gene expression among the most affected processes.

   VO2max ranged 18.4 to 40.0 mL•min^-1•kg^-1. DEGs whose log2 fold change correlated with VO2max (linear correlation, unadjusted p < 0.05) went from 3 at MID to 5,803 at +24 h and 1,733 at +48 h, mostly with larger changes at lower fitness; ribosomal biogenesis was the top enrichment at +24 and +48 h. Approximately 60% of all DEGs correlated with VO2max at one or more time points or a gene feature. · Higher cardiorespiratory fitness blunts the…; Minimal effect of sex on exercise-induced gene…; Statistical analysis

4. SuggestedMost mitochondrial genes respond to exercise, but mainly by downregulation at +24 and +48 h, with members of the same pathway spread over six temporal clusters; the authors infer substantial post-transcriptional control of mitochondrial adaptation.

   1,037 of 1,136 MitoCarta3.0 genes (91%) were differentially expressed; 565 (50% of all mitochondrial genes) had not been reported as exercise-responsive. Upregulated mitochondrial DEGs peaked at +12 h, downregulated ones at +24 and +48 h, where they formed the majority. Six mfuzz clusters split every pathway; mRNA showed no consistent match to training-induced protein changes (Granata et al.). · Mitochondrial gene expression is primarily…; Figure legends

5. ShownAlthough 1,193 genes differ by sex at rest, the exercise response is almost the same in fitness-matched males and females; the authors attribute sex-only DEGs largely to lower per-sex statistical power.

   At baseline 1,193 genes (6.9%) differed by sex (675 higher in males, 518 in females), over-representing X (10.6% of detected X genes) and Y (100%). After exercise 14,662 DEGs were shared, 810 male-only and 987 female-only, the sex-only ones with smaller mean log2 fold changes. Directly comparing responses, only SNX30, DNMBP, DAAM2-AS1 and CTIF of 17,345 genes differed; AUC analysis found no sex differences. · Minimal effect of sex on exercise-induced gene…; Figure legends