Muscle Transcriptional Networks Linked to Resistance Exercise Training Hypertrophic Response Heterogeneity

Author(s):  
Kaleen M. Lavin ◽  
Margaret B. Bell ◽  
Jeremy S. McAdam ◽  
Bailey D Peck ◽  
R. Grace Walton ◽  
...  

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as (i) predictive of hypertrophy, (ii) responsive to RT independent of muscle hypertrophy, or (iii) plastic with hypertrophy. Older adults (n=31, 18F/13M, 70±4y) underwent 14-wk RT (3d/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome], and thigh lean mass [dual-energy x-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n=31) and post-RT (n=22). Prediction networks (using only baseline RNAseq) were identified by Weighted Gene Correlation Network Analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-Level Information ExtractoR (PLIER) was applied to identify Response networks and link genes to biological annotation. Predictionnetworks (n=6) confirmed transcripts previously connected to resistance/ aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n=6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that inter-individual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity.

1990 ◽  
Vol 69 (2) ◽  
pp. 434-437 ◽  
Author(s):  
K. E. Yarasheski ◽  
P. W. Lemon ◽  
J. Gilloteaux

The purpose of this investigation was to determine whether heavy-resistance exercise training alters the skeletal muscle fiber composition of young rats. Ten male Long Evans rats (3 wk old) were trained to lift progressively heavier weights, which were secured to the rats' tails, while they ascended a 40-cm 90 degree mesh incline 20 times/day 5 days/wk for a food reward. After 8 wk of training, they lifted 406 +/- 19 (SD) g in addition to their body weight (261 +/- 9 g). Compared with 10 sedentary pair-fed rats, no hypertrophy of forelimb muscles (biceps brachii and brachialis) was observed, but rectus femoris wet and dry weights were greater (P less than 0.01) in the trained group. In the deep region of the rectus femoris, type I fiber area was similar between groups, but the trained rats had both a lower (P less than 0.05) percentage of type I fibers and a smaller (P less than 0.05) portion of the total area occupied by type I fibers. The percentage of type IIb fibers in the deep region of the rectus femoris was also similar between groups, but the portion of the deep area composed of type IIb fibers was greater (P less than 0.05) in the trained rats. In the superficial region of the rectus femoris, the trained rats' type IIb fibers were larger (P less than 0.01) and occupied a greater (P less than 0.05) portion of the superficial muscle area.(ABSTRACT TRUNCATED AT 250 WORDS)


2018 ◽  
Vol 124 (4) ◽  
pp. 888-898 ◽  
Author(s):  
Neil A. Kelly ◽  
Kelley G. Hammond ◽  
C. Scott Bickel ◽  
Samuel T. Windham ◽  
S. Craig Tuggle ◽  
...  

Aging muscle atrophy is in part a neurodegenerative process revealed by denervation/reinnervation events leading to motor unit remodeling (i.e., myofiber type grouping). However, this process and its physiological relevance are poorly understood, as is the wide-ranging heterogeneity among aging humans. Here, we attempted to address 1) the relation between myofiber type grouping and molecular regulators of neuromuscular junction (NMJ) stability; 2) the impact of motor unit remodeling on recruitment during submaximal contractions; 3) the prevalence and impact of motor unit remodeling in Parkinson’s disease (PD), an age-related neurodegenerative disease; and 4) the influence of resistance exercise training (RT) on regulators of motor unit remodeling. We compared type I myofiber grouping, molecular regulators of NMJ stability, and the relative motor unit activation (MUA) requirement during a submaximal sit-to-stand task among untrained but otherwise healthy young (YA; 26 yr, n = 27) and older (OA; 66 yr, n = 91) adults and OA with PD (PD; 67 yr, n = 19). We tested the effects of RT on these outcomes in OA and PD. PD displayed more motor unit remodeling, alterations in NMJ stability regulation, and a higher relative MUA requirement than OA, suggesting PD-specific effects. The molecular and physiological outcomes tracked with the severity of type I myofiber grouping. Together these findings suggest that age-related motor unit remodeling, manifested by type I myofiber grouping, 1) reduces MUA efficiency to meet submaximal contraction demand, 2) is associated with disruptions in NMJ stability, 3) is further impacted by PD, and 4) may be improved by RT in severe cases. NEW & NOTEWORTHY Because the physiological consequences of varying amounts of myofiber type grouping are unknown, the current study aims to characterize the molecular and physiological correlates of motor unit remodeling. Furthermore, because exercise training has demonstrated neuromuscular benefits in aged humans and improved innervation status and neuromuscular junction integrity in animals, we provide an exploratory analysis of the effects of high-intensity resistance training on markers of neuromuscular degeneration in both Parkinson’s disease (PD) and age-matched older adults.


2021 ◽  
Vol 7 ◽  
Author(s):  
Paul A. Roberson ◽  
C. Brooks Mobley ◽  
Matthew A. Romero ◽  
Cody T. Haun ◽  
Shelby C. Osburn ◽  
...  

Introduction: Amino acid transporters are essential for cellular amino acid transport and promoting protein synthesis. While previous literature has demonstrated the association of amino acid transporters and protein synthesis following acute resistance exercise and amino acid supplementation, the chronic effect of resistance exercise and supplementation on amino acid transporters is unknown. The purpose herein was to determine if amino acid transporters and amino acid metabolic enzymes were related to skeletal muscle hypertrophy following resistance exercise training with different nutritional supplementation strategies.Methods: 43 college-aged males were separated into a maltodextrin placebo (PLA, n = 12), leucine (LEU, n = 14), or whey protein concentrate (WPC, n = 17) group and underwent 12 weeks of total-body resistance exercise training. Each group's supplement was standardized for total energy and fat, and LEU and WPC supplements were standardized for total leucine (6 g/d). Skeletal muscle biopsies were obtained prior to training and ~72 h following each subject's last training session.Results: All groups increased type I and II fiber cross-sectional area (fCSA) following training (p < 0.050). LAT1 protein increased following training (p < 0.001) and increased more in PLA than LEU and WPC (p < 0.050). BCKDHα protein increased and ATF4 protein decreased following training (p < 0.001). Immunohistochemistry indicated total LAT1/fiber, but not membrane LAT1/fiber, increased with training (p = 0.003). Utilizing all groups, the change in ATF4 protein, but no other marker, trended to correlate with the change in fCSA (r = 0.314; p = 0.055); however, when regression analysis was used to delineate groups, the change in ATF4 protein best predicted the change in fCSA only in LEU (r2 = 0.322; p = 0.043). In C2C12 myoblasts, LAT1 protein overexpression caused a paradoxical decrease in protein synthesis levels (p = 0.002) and decrease in BCKDHα protein (p = 0.001).Conclusions: Amino acid transporters and metabolic enzymes are affected by resistance exercise training, but do not appear to dictate muscle fiber hypertrophy. In fact, overexpression of LAT1 in vitro decreased protein synthesis.


2002 ◽  
Vol 283 (2) ◽  
pp. R408-R416 ◽  
Author(s):  
Jeffrey J. Widrick ◽  
Julian E. Stelzer ◽  
Todd C. Shoepe ◽  
Dena P. Garner

The aim of this study was to assess the relationships between human muscle fiber hypertrophy, protein isoform content, and maximal Ca2+-activated contractile function following a short-term period of resistance exercise training. Six male subjects (age 27 ± 2 yr) participated in a 12-wk progressive resistance exercise training program that increased voluntary lower limb extension strength by >60%. Single chemically skinned fibers were prepared from pre- and posttraining vastus lateralis muscle biopsies. Training increased the cross-sectional area (CSA) and peak Ca2+-activated force (Po) of fibers containing type I, IIa, or IIa/IIx myosin heavy chain by 30–40% without affecting fiber-specific force (Po/CSA) or unloaded shortening velocity (Vo). Absolute fiber peak power rose as a result of the increase in Po, whereas power normalized to fiber volume was unchanged. At the level of the cross bridge, the effects of short-term resistance training were quantitative (fiber hypertrophy and proportional increases in fiber Po and absolute power) rather than qualitative (no change in Po/CSA, Vo, or power/fiber volume).


Sign in / Sign up

Export Citation Format

Share Document