Browsing by Author "Mobley, Christopher B"
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Item Open Access An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.(FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021-05) Vann, Christopher G; Morton, Robert W; Mobley, Christopher B; Vechetti, Ivan J; Ferguson, Brian K; Haun, Cody T; Osburn, Shelby C; Sexton, Casey L; Fox, Carlton D; Romero, Matthew A; Roberson, Paul A; Oikawa, Sara Y; McGlory, Chris; Young, Kaelin C; McCarthy, John J; Phillips, Stuart M; Roberts, Michael DWe examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.Item Open Access Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training(PLOS ONE) Mobley, Christopher B; Haun, Cody T; Roberson, Paul A; Mumford, Petey W; Kephart, Wesley C; Romero, Matthew A; Osburn, Shelby C; Vann, Christopher G; Young, Kaelin C; Beck, Darren T; Martin, Jeffrey S; Lockwood, Christopher M; Roberts, Michael DItem Open Access Effects of Graded Whey Supplementation During Extreme-Volume Resistance Training(Frontiers in Nutrition) Haun, Cody T; Vann, Christopher G; Mobley, Christopher B; Roberson, Paul A; Osburn, Shelby C; Holmes, Hudson M; Mumford, Petey M; Romero, Matthew A; Young, Kaelin C; Moon, Jordan R; Gladden, L Bruce; Arnold, Robert D; Israetel, Michael A; Kirby, Annie N; Roberts, Michael DItem Open Access Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders to Resistance Exercise Training: Current Perspectives and Future Research Directions(Frontiers in Physiology) Roberts, Michael D; Haun, Cody T; Mobley, Christopher B; Mumford, Petey W; Romero, Matthew A; Roberson, Paul A; Vann, Christopher G; McCarthy, John JItem Open Access Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats(American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2019-09-01) Mumford, Petey W; Romero, Matthew A; Osburn, Shelby C; Roberson, Paul A; Vann, Christopher G; Mobley, Christopher B; Brown, Michael D; Kavazis, Andreas N; Young, Kaelin C; Roberts, Michael DLong interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old ( n = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher ( P < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNA-sequencing indicated mRNAs related to DNA methylation ( Tet1) and histone acetylation ( Hdac2) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats ( P < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility.Item Open Access Skeletal muscle mitochondrial volume and myozenin-1 protein differences exist between high versus low anabolic responders to resistance training(PeerJ) Roberts, Michael D; Romero, Matthew A; Mobley, Christopher B; Mumford, Petey W; Roberson, Paul A; Haun, Cody T; Vann, Christopher G; Osburn, Shelby C; Holmes, Hudson H; Greer, Rory A; Lockwood, Christopher M; Parry, Hailey A; Kavazis, Andreas NBackgroundWe sought to examine how 12 weeks of resistance exercise training (RET) affected skeletal muscle myofibrillar and sarcoplasmic protein levels along with markers of mitochondrial physiology in high versus low anabolic responders.MethodsUntrained college-aged males were classified as anabolic responders in the top 25th percentile (high-response cluster (HI);n= 13, dual x-ray absorptiometry total body muscle mass change (Δ) = +3.1 ± 0.3 kg, Δ vastus lateralis (VL) thickness = +0.59 ± 0.05 cm, Δ muscle fiber cross sectional area = +1,426 ± 253 μm2) and bottom 25th percentile (low-response cluster (LO);n= 12, +1.1 ± 0.2 kg, +0.24 ± 0.07 cm, +5 ± 209 μm2;p< 0.001 for all Δ scores compared to HI). VL muscle prior to (PRE) and following RET (POST) was assayed for myofibrillar and sarcoplasmic protein concentrations, myosin and actin protein content, and markers of mitochondrial volume. Proteins related to myofibril formation, as well as whole lysate PGC1-α protein levels were assessed.ResultsMain effects of cluster (HI > LO,p= 0.018, Cohen’sd= 0.737) and time (PRE > POST,p= 0.037, Cohen’sd= −0.589) were observed for citrate synthase activity, although no significant interaction existed (LO PRE = 1.35 ± 0.07 mM/min/mg protein, LO POST = 1.12 ± 0.06, HI PRE = 1.53 ± 0.11, HI POST = 1.39 ± 0.10). POST myofibrillar myozenin-1 protein levels were up-regulated in the LO cluster (LO PRE = 0.96 ± 0.13 relative expression units, LO POST = 1.25 ± 0.16, HI PRE = 1.00 ± 0.11, HI POST = 0.85 ± 0.12; within-group LO increasep= 0.025, Cohen’sd= 0.691). No interactions or main effects existed for other assayed markers.DiscussionOur data suggest myofibrillar or sarcoplasmic protein concentrations do not differ between HI versus LO anabolic responders prior to or following a 12-week RET program. Greater mitochondrial volume in HI responders may have facilitated greater anabolism, and myofibril myozenin-1 protein levels may represent a biomarker that differentiates anabolic responses to RET. However, mechanistic research validating these hypotheses is needed.Item Open Access Synergist ablation-induced hypertrophy occurs more rapidly in the plantaris than soleus muscle in rats due to different molecular mechanisms(American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2020-02-01) Roberts, Michael D; Mobley, Christopher B; Vann, Christopher G; Haun, Cody T; Schoenfeld, Brad J; Young, Kaelin C; Kavazis, Andreas NWe examined molecular mechanisms that were altered during rapid soleus (type I fiber-dominant) and plantaris (type II fiber-dominant) hypertrophy in rats. Twelve Wistar rats (3.5 mo old; 6 female, 6 male) were subjected to surgical right-leg soleus and plantaris dual overload [synergist ablation (SA)], and sham surgeries were performed on left legs (CTL). At 14 days after surgery, the muscles were dissected. Plantaris mass was 27% greater in the SA than CTL leg ( P < 0.001), soleus mass was 13% greater in the SA than CTL leg ( P < 0.001), and plantaris mass was higher than soleus mass in the SA leg ( P = 0.001). Plantaris total RNA concentrations and estimated total RNA levels (suggestive of ribosome density) were 19% and 47% greater in the SA than CTL leg ( P < 0.05), protein synthesis levels were 64% greater in the SA than CTL leg ( P = 0.038), and satellite cell number per fiber was 60% greater in the SA than CTL leg ( P = 0.003); no differences in these metrics were observed between soleus SA and CTL legs. Plantaris, as well as soleus, 20S proteasome activity was lower in the SA than CTL leg ( P < 0.05), although the degree of downregulation was greater in the plantaris than soleus muscle (−63% vs. −20%, P = 0.001). These data suggest that early-phase plantaris hypertrophy occurs more rapidly than soleus hypertrophy, which coincided with greater increases in ribosome biogenesis, protein synthesis, and satellite cell density, as well as greater decrements in 20S proteasome activity, in the plantaris muscle.