Andrew P. Garnham

Ribosome biogenesis adaptation and mTORC1 signalling in human skeletal muscle following concurrent training compared with resistance training alone

Combining RT with endurance training (i.e., concurrent training) may attenuate skeletal muscle hypertrophy consequent to RT; however, the underlying mechanisms are unclear. We investigated whether markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, are attenuated following concurrent training vs. RT alone. Twenty-three males (mean ± SD: age, 29.6 ± 5.5 y; V̇O2peak, 44 ± 11 mL-kg−1min−1) underwent 8 wk (3 sessions-wk−1) of either: 1) HIT (high-intensity interval training) combined with RT (HIT+RT group, n=8), 2) work-matched MICT (moderate-intensity continuous training) combined with RT (MICT+RT group, n=7), or 3) RT alone (RT group, n=8). Vastus lateralis biopsies were obtained before training, and immediately before, 1 h and 3 h after the final training session. Type I muscle fibre cross-sectional area (CSA) was further increased by RT vs. HIT+RT (34 ±22%; ES, 1.03 ±0.80), but not vs. MICT+RT (15 ±54%; ES, 0.39 ±1.45). Basal training-induced changes in expression of the 45S ribosomal RNA (rRNA) precursor, and 5.8S and 28S mature rRNAs were greater for concurrent exercise vs. RT, largely because of trends for reduced rRNA expression following RT. During the final training session, RT further increased skeletal muscle mTORC1 signalling (p70S6K1 and rps6 phosphorylation) and signalling related to 45S rRNA transcription (TIF-1A and UBF phosphorylation) vs. concurrent exercise. Thus, when performed in a training-accustomed state, RT preferentially induces mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle vs. concurrent exercise. However, changes in markers of skeletal muscle ribosome biogenesis were more favourable with concurrent training vs. RT. Table of contents category: Muscle 1. Key points summary Ribosome biogenesis is an important process linked with human skeletal muscle growth following resistance training (RT); however, whether concurrent training alters skeletal muscle ribosome biogenesis compared with RT alone in unknown In agreement with previous studies, concurrent training blunted the RT-induced increase in type I, but not type II, muscle fibre size Despite the attenuated muscle hypertrophy with concurrent training, changes in markers of skeletal muscle ribosome biogenesis were generally more favourable with concurrent training vs. RT performed alone Conversely, a single session of resistance exercise (RE) performed post-training was more potent for inducing signalling responses in skeletal muscle related to both ribosome biogenesis and the mTORC1 pathway, vs. concurrent exercise Ribosome biogenesis is therefore not compromised following short-term concurrent training; however, both mTORC1 and ribosome biogenesis-related signalling are attenuated in skeletal muscle following a single session of concurrent exercise performed in a training-accustomed state 3. Abbreviations list 1-RM one-repetition maximum 4E-BP1 eukaryotic initiation factor 4E binding protein 1 AMPK 5’ adenosine monophosphate-activated protein kinase β2M beta-2 microglobulin CDK cyclin-dependent kinase DXA dual-energy x-ray absorptiometry Fox-O1 forkhead box-O1 GAPDH glyceraldehyde 3-phosphate dehydrogenase HIT high-intensity interval training cycling LT lactate threshold MICT moderate-intensity continuous cycling MPS muscle protein synthesis mRNA messenger RNA mTORC1 mechanistic target or rapamycin complex 1 MuRF-1 muscle RING-finger 1 p70S6K1 70 kilodalton ribosomal protein subunit kinase 1 PGC-1α peroxisome proliferator activated receptor gamma co-activator 1 alpha POLR1B polymerase (RNA) 1 polypeptide B RE resistance exercise RPE rating of perceived exertion rRNA ribosomal ribonucleic acid RT resistance training SL-1 selectivity factor-1 TBP TATA binding protein TIF-1A RRN3 polymerase 1 transcription factor UBF upstream binding factor V̇O2peak peak volume of oxygen uptake Wpeak peak aerobic power.Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT performed alone. Twenty-three recreationally-active males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor, and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT alone. However, during the final training session, RT induced further increases in both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT preferentially induces mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in skeletal muscle ribosome biogenesis markers were more favourable following concurrent training versus RT performed alone.

ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P < 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 < P < 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P < 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P < 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.

The effect of acute and short term glucocorticoid administration on exercise capacity and metabolism

OBJECTIVESnGlucocorticoids (GC) are commonly used in the treatment of inflammatory conditions. Chronic GC administration has severe side effects that can decrease exercise capacity and, as a result performance. The side effects of acute (single dose) and short term (<7 days) GC administration are less severe, therefore the impact on exercise performance is unclear. Consequently, it is of interest to determine the influence of acute and short term GC administration on exercise capacity and performance and investigate the relationship with metabolism.nnnDESIGNnReview article.nnnMETHODSnIncluded in the review were studies with healthy volunteers that reported exercise capacity and performance outcomes following acute and short term GC ingestion. Additionally, the relationship of exercise, GC ingestion and metabolism was investigated.nnnRESULTSnAcute GC treatment appears to have minimal effects on exercise performance at intensities between 60 and 90% of VO2max. Short term GC treatment improved performance in the majority of studies at various exercise intensities. In general, blood glucose values increased whilst insulin and lactate values remained unchanged following GC administration. However, inconsistencies in metabolic results are present and may be due to variations in exercise protocols and the type and dosage of drug treatments.nnnCONCLUSIONSnAcute GC administration has a minimal effect on exercise capacity and performance while short-term GC administration is likely to improve performance. Future studies should focus on the effects of GC on exercise performance and exercise metabolism during and post exercise to determine the effects on exercise capacity.

P-86 The use of whole-genome expression to predict exercise training response in the gene smart study: preliminary results

Differences in gene expression patterns may explain, at least partly, the inter-individual variability in response to similar exercise training [1, 2]. Studies such as the Gene Skeletal Muscle Adaptive Response to Training (SMART) study (www.athlomeconsortium.org) are necessary to elucidate the molecular mechanisms underlying those individual responses. Here we examine the individual differences in gene expression following exercise and training in the Gene SMART study. Twenty-two moderately trained, healthy Caucasians participants (all males 20-45 y, BMI ≤ 30) completed a single session of High Intensity Interval Exercise (HIIE) on a cycle ergometer (8 × 2-min intervals at 85% of maximal power with 1 min of recovery between intervals), and a subset of those participants (n = 13) completed four weeks of High Intensity Interval Training (HIIT). Blood samples were collected before, immediately after HIIE, 3 h post HIIE and four weeks post HIIT. Total RNA extracted from whole blood was used for whole transcriptome analysis (GeneChip HTA 2.0 from Affymetrix UK Ltd, > 285,000 full-length transcripts). One-way repeated measures ANOVA analysis was used to identify differential expressed genes at those four time points. Changes considered significant at a 5% FDR and a fold change (FC) of 2. Compared to baseline, 123 genes were differentially expressed immediately post HIIE whereas 204 genes were differentially expressed 3 hours post HIIE (n = 22). Specifically, 34 genes were upregulated and 89 genes were downregulated immediately post HIIE, whereas 23 genes were upregulated and 181 were downregulated 3 hours post HIIE. Four transcripts overlapped between those two time points; RUNX3 and CTSW expression was significantly increased immediately post HIIE (FC = 2.6, FDR adj.p=0.007 and FC = 2.4, FDR adj.p=0.005, respectively), and significantly decreased 3 hours post HIIE (FC = −2.2, FDR adj.p=0.002 and FC = −2.1, FDR adj.p=0.003, respectively), compared to baseline. Additionally, the gene expression levels of TC21000168.hg.1 and TC21000719.hg.1 were significantly decreased (FC = −2.1, FDR adj.p=0.005 and FC = −2.1, FDR adj.p=0.007) immediately post HIIE and significantly increased 3 hours post HIIE (FC = 2.7, FDR adj.p=0.0003 and FC = 2.7, FDR adj.p=0.0003). No significant changes in gene expression were found after 4 weeks of HIIT compared to baseline (n = 13). Although a relatively small sample size, this preliminary whole-genome expression analysis from whole blood is encouraging and supports the idea of using molecular markers such as gene expression to predict individual response to exercise. More participants are currently being recruited to increase the sample size. References Bouchard C, et al. Genomic predictors of the maximal O(2) uptake response to standardised exercise training programs. J Appl Physiol 1985, 2011.110(5):1160–70. Timmons JA, et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 1985, 2010;108(6):1487–96.