bims-exemet 2021-05-02 papers

Issue of 2021–05–02
seven papers selected by
Javier Botella Ruiz, Victoria University

J Physiol. 2021 Apr 29.

Genetic and epigenetic regulation of skeletal muscle ribosome biogenesis with exercise.

Vandré C Figueiredo, Yuan Wen, Björn Alkner, Rodrigo Fernandez-Gonzalo, Jessica Norrbom, Ivan J Vechetti, Taylor Valentino, C Brooks Mobley, Gabriel E Zentner, Charlotte A Peterson, John J McCarthy, Kevin A Murach, Ferdinand von Walden.

KEY POINTS: Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise (EE) in human skeletal muscle throughout a 24-hour time-course of recovery. A PCR-based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE. Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer, and non-canonical MYC-associated regions, but not the promoter. Myonuclear-specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans. A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage.
ABSTRACT: Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, but the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time-course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31±8 yrs, 25±4 kg/m2 ) at rest and 30 min, 3h, 8h, and 24h after acute endurance (n = 10, 45 min cycling, 70% VO2 max) or resistance exercise (n = 10, 4×7×2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using qPCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER, and global rDNA CpG methylation was assessed using reduced-representation bisulfite sequencing. Ribosome biogenesis and MYC transcription were associated primarily with resistance but not endurance exercise, indicating preferential upregulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labeling and genetic myonuclear fluorescent labeling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. This study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation. This article is protected by copyright. All rights reserved.

Keywords: CpG methylation; Myc; enhancer; intergenic spacer; rDNA; rDNA copy number

DOI: https://doi.org/10.1113/JP281244

Front Sports Act Living. 2021 ;3 660291

Post-exercise Cold Water Immersion Effects on Physiological Adaptations to Resistance Training and the Underlying Mechanisms in Skeletal Muscle: A Narrative Review.

Aaron C Petersen, Jackson J Fyfe.

Post-exercise cold-water immersion (CWI) is a popular recovery modality aimed at minimizing fatigue and hastening recovery following exercise. In this regard, CWI has been shown to be beneficial for accelerating post-exercise recovery of various parameters including muscle strength, muscle soreness, inflammation, muscle damage, and perceptions of fatigue. Improved recovery following an exercise session facilitated by CWI is thought to enhance the quality and training load of subsequent training sessions, thereby providing a greater training stimulus for long-term physiological adaptations. However, studies investigating the long-term effects of repeated post-exercise CWI instead suggest CWI may attenuate physiological adaptations to exercise training in a mode-specific manner. Specifically, there is evidence post-exercise CWI can attenuate improvements in physiological adaptations to resistance training, including aspects of maximal strength, power, and skeletal muscle hypertrophy, without negatively influencing endurance training adaptations. Several studies have investigated the effects of CWI on the molecular responses to resistance exercise in an attempt to identify the mechanisms by which CWI attenuates physiological adaptations to resistance training. Although evidence is limited, it appears that CWI attenuates the activation of anabolic signaling pathways and the increase in muscle protein synthesis following acute and chronic resistance exercise, which may mediate the negative effects of CWI on long-term resistance training adaptations. There are, however, a number of methodological factors that must be considered when interpreting evidence for the effects of post-exercise CWI on physiological adaptations to resistance training and the potential underlying mechanisms. This review outlines and critiques the available evidence on the effects of CWI on long-term resistance training adaptations and the underlying molecular mechanisms in skeletal muscle, and suggests potential directions for future research to further elucidate the effects of CWI on resistance training adaptations.

Keywords: adaptation; cold-water immersion; exercise performance; molecular responses; resistance exercise; skeletal muscle

DOI: https://doi.org/10.3389/fspor.2021.660291

Int J Mol Sci. 2021 Apr 27. pii: 4577. [Epub ahead of print]22(9):

Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.

Laia Just-Borràs, Víctor Cilleros-Mañé, Erica Hurtado, Olivier Biondi, Frédéric Charbonnier, Marta Tomàs, Neus Garcia, Josep Tomàs, Maria A Lanuza.

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes' fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.

Keywords: BDNF/TrkB signaling; endurance exercise; neuromuscular junction; new activity conditions; skeletal muscle

DOI: https://doi.org/10.3390/ijms22094577

Scand J Med Sci Sports. 2021 Apr 26.

Intra-individual differences in the effect of endurance vs. Resistance training on vascular function: a cross-over study.

Ellen Adele Dawson, Bahare Sheikhsaraf, Maxime Boidin, Robert M Erskine, Dick Hj Thijssen.

We used a within-subject, cross-over design study to compare the impact of 4-weeks' resistance (RT) versus endurance (END) training on vascular function. We subsequently explored the association of intra-individual effects of RT versus END on vascular function with a single nucleotide polymorphism (SNP) of the NOS3 gene. Thirty-five healthy males (21±2 years old) were genotyped for the NOS3 rs2070744 SNP and completed both training modalities. Participants completed 12 sessions over a 4-week period, either RT (leg-extension) or END (cycling) training in a randomised, balanced cross-over design with a 3 week washout period. Participants performed peak oxygen uptake (peak V˙ O2 ) and leg-extension single-repetition maximum (1-RM) testing, and vascular function assessment using flow-mediated dilation (FMD) on 3 separated days pre/post training. Peak V˙ O2 increased after END (P<0.001), while 1-RM increased after RT (P<0.001). FMD improved after 4-weeks' training (time-effect: P=0.006), with no difference between exercise modalities (interaction-effect: P=0.92). No relation was found between individual changes (delta, pre-post) in FMD to both types of training (R2 =0.06, P=0.14). Intra-individual changes in FMD following END and RT were associated with the NOS3 SNP, with TT homozygotes significantly favouring only END (P=0.016) and TC/CC tending to favour RT only (P=0.056). Although both training modes improved vascular function, significant intra-individual variation in the adaptation of FMD was found. The association with NOS3 genotype suggests a genetic predisposition to FMD adapting to a specific mode of chronic exercise. This study therefore provides novel evidence for personalised exercise training to optimise vascular health.

Keywords: Endothelial function; aerobic training; genetics; response to training; strength training; trainability

DOI: https://doi.org/10.1111/sms.13975

Cells. 2021 Apr 26. pii: 1022. [Epub ahead of print]10(5):

Exercise Training-Induced Extracellular Matrix Protein Adaptation in Locomotor Muscles: A Systematic Review.

Efpraxia Kritikaki, Rhiannon Asterling, Lesley Ward, Kay Padget, Esther Barreiro, Davina C M Simoes.

Exercise training promotes muscle adaptation and remodelling by balancing the processes of anabolism and catabolism; however, the mechanisms by which exercise delays accelerated muscle wasting are not fully understood. Intramuscular extracellular matrix (ECM) proteins are essential to tissue structure and function, as they create a responsive environment for the survival and repair of the muscle fibres. However, their role in muscle adaptation is underappreciated and underinvestigated. The PubMed, COCHRANE, Scopus and CIHNAL databases were systematically searched from inception until February 2021. The inclusion criteria were on ECM adaptation after exercise training in healthy adult population. Evidence from 21 studies on 402 participants demonstrates that exercise training induces muscle remodelling, and this is accompanied by ECM adaptation. All types of exercise interventions promoted a widespread increase in collagens, glycoproteins and proteoglycans ECM transcriptomes in younger and older participants. The ECM controlling mechanisms highlighted here were concerned with myogenic and angiogenic processes during muscle adaptation and remodelling. Further research identifying the mechanisms underlying the link between ECMs and muscle adaptation will support the discovery of novel therapeutic targets and the development of personalised exercise training medicine.

Keywords: adaptation; ageing; collagens; exercise training; extracellular matrix; glycoproteins; myogenesis; proteoglycans; remodelling; skeletal muscle

DOI: https://doi.org/10.3390/cells10051022

Sports Med. 2021 Apr 26.

Muscle Glycogen Metabolism and High-Intensity Exercise Performance: A Narrative Review.

Jeppe F Vigh-Larsen, Niels Ørtenblad, Lawrence L Spriet, Kristian Overgaard, Magni Mohr.

Muscle glycogen is the main substrate during high-intensity exercise and large reductions can occur after relatively short durations. Moreover, muscle glycogen is stored heterogeneously and similarly displays a heterogeneous and fiber-type specific depletion pattern with utilization in both fast- and slow-twitch fibers during high-intensity exercise, with a higher degradation rate in the former. Thus, depletion of individual fast- and slow-twitch fibers has been demonstrated despite muscle glycogen at the whole-muscle level only being moderately lowered. In addition, muscle glycogen is stored in specific subcellular compartments, which have been demonstrated to be important for muscle function and should be considered as well as global muscle glycogen availability. In the present review, we discuss the importance of glycogen metabolism for single and intermittent bouts of high-intensity exercise and outline possible underlying mechanisms for a relationship between muscle glycogen and fatigue during these types of exercise. Traditionally this relationship has been attributed to a decreased ATP resynthesis rate due to inadequate substrate availability at the whole-muscle level, but emerging evidence points to a direct coupling between muscle glycogen and steps in the excitation-contraction coupling including altered muscle excitability and calcium kinetics.

DOI: https://doi.org/10.1007/s40279-021-01475-0