Skeletal muscle myosin heavy chain protein fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

We sought to examine how resistance exercise (RE), cycling exercise, and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation in humans. In the first study (1boutRE), younger adult men (n=8; 5±2 years of RE experience) performed a lower body RE bout with vastus lateralis (VL) biopsies obtained immediately before, 3-, and 6-hours post-exercise. In the second study (10weekRT), VL biopsies were obtained in untrained younger adults (n=36, 18 men and 18 women) before and 24 hours (24h) after their first/naïve RE bout. These participants also engaged in 10 weeks (24 sessions) of resistance training and donated VL biopsies before and 24h after their last RE bout. VL biopsies were also examined from a third acute cycling study (n=7) and a fourth study involving two weeks of leg immobilization (n=20, 15 men and 5 women) to determine how MyHC fragmentation was affected. In the 1boutRE study, the fragmentation of all MyHC isoforms (MyHCTotal) increased 3 hours post-RE (~ +200%, p=0.018) and returned to pre-exercise levels by 6 hours post-RE. Immunoprecipitation of MyHCTotal revealed ubiquitination levels remained unaffected at the 3- and 6-hour post-RE time points. Interestingly, a greater increase in magnitude for MyHC type IIa versus I isoform fragmentation occurred 3-hours post-RE (8.6±6.3-fold versus 2.1±0.7-fold, p=0.018). In all 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24h post-RE (+65% and +36%, respectively; p<0.001); however, the last RE bout response was attenuated compared to the first bout (p=0.045). The first/naïve bout response was significantly elevated in females only (p<0.001), albeit females also demonstrated a last bout attenuation response (p=0.002). Although an acute cycling bout did not alter MyHCTotal fragmentation, ~8% VL atrophy with two weeks of leg immobilization led to robust MyHCTotal fragmentation (+108%, p<0.001), and no sex-based differences were observed. In summary, RE and disuse atrophy increase MyHC protein fragmentation. A dampened response with 10 weeks of resistance training, and more refined responses in well-trained men, suggest this is an adaptive process. Given the null polyubiquitination IP findings, more research is needed to determine how MyHC fragments are processed. Moreover, further research is needed to determine how aging and disease-associated muscle atrophy affect these outcomes, and whether MyHC fragmentation is a viable surrogate for muscle protein turnover rates.

Acute and Chronic Changes in Muscle Androgen Receptor Markers Are Not Associated with Muscle Hypertrophy in Women and Men.

PURPOSE: Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes. METHODS: Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound. RESULTS: At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men. CONCLUSIONS: Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.

Resistance training-induced changes in muscle proteolysis and extracellular matrix remodeling biomarkers in the untrained and trained states.

PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period. RESULTS: There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged. CONCLUSION: Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.

Muscle Hypertrophy Is Affected by Volume Load Progression Models.

ABSTRACT: Nóbrega, SR, Scarpelli, MC, Barcelos, C, Chaves, TS, and Libardi, CA. Muscle hypertrophy is affected by volume load progression models. J Strength Cond Res 37(1): 62-67, 2023-This exploratory secondary data analysis compared the effects of a percentage of 1 repetition maximum (%1RM) and a repetition zone (RM Zone) progression model carried out to muscle failure on volume load progression (VLPro), muscle strength, and cross-sectional area (CSA). The sample comprised 24 untrained men separated in 2 groups: %1RM (n = 14) and RM Zone (n = 10). Muscle CSA and muscle strength (1RM) were assessed before and after 24 training sessions, and an analysis of covariance was used. Volume load progression and accumulated VL (VLAccu) were compared between groups. The relationships between VLProg, VLAccu, 1RM, and CSA increases were also investigated. A significance level of p ≤ 0.05 was adopted for all statistical procedures. Volume load progression was greater for RM Zone compared with %1RM (2.30 ± 0.58% per session vs. 1.01 ± 0.55% per session; p < 0.05). Significant relationships were found between 1RM and VLProg (p < 0.05) and CSA and VLProg (p < 0.05). No between-group differences were found for VLAccu (p > 0.05). Analysis of covariance revealed no between-group differences for 1RM absolute (p < 0.05) or relative changes (p < 0.05). However, post hoc testing revealed greater absolute and relative changes in CSA for the RM Zone group compared with the %1RM group (p < 0.001). In conclusion, RM Zone resulted in a greater VLPro rate and muscle CSA gains compared with %1RM, with no differences in VLAccu and muscle strength gains between progression models.

Muscle Hypertrophy Response Is Affected by Previous Resistance Training Volume in Trained Individuals.

ABSTRACT: Scarpelli, MC, Nóbrega, SR, Santanielo, N, Alvarez, IF, Otoboni, GB, Ugrinowitsch, C, and Libardi, CA. Muscle hypertrophy response is affected by previous resistance training volume in trained individuals. J Strength Cond Res 36(4): 1153-1157, 2022-The purpose of this study was to compare gains in muscle mass of trained individuals after a resistance training (RT) protocol with standardized (i.e., nonindividualized) volume (N-IND), with an RT protocol using individualized volume (IND). In a within-subject approach, 16 subjects had one leg randomly assigned to N-IND (22 sets·wk-1, based on the number of weekly sets prescribed in studies) and IND (1.2 × sets·wk-1 recorded in training logs) protocols. Muscle cross-sectional area (CSA) was assessed by ultrasound imaging at baseline (Pre) and after 8 weeks (Post) of RT, and the significance level was set at p < 0.05. Changes in the vastus lateralis CSA (difference from Pre to Post) were significantly higher for the IND protocol (p = 0.042; mean difference: 1.08 cm2; confidence interval [CI]: 0.04-2.11). The inferential analysis was confirmed by the CI of the effect size (0.75; CI: 0.03-1.47). Also, the IND protocol had a higher proportion of individuals with greater muscle hypertrophy than the typical error of the measurement (chi-square, p = 0.0035; estimated difference = 0.5, CI: 0.212-0.787). In conclusion, individualizing the weekly training volume of research protocols provides greater gains in muscle CSA than prescribing a group standard RT volume.

Effect of resistance training to muscle failure vs non-failure on strength, hypertrophy and muscle architecture in trained individuals.

The aim of this study was to compare the effects of resistance training to muscle failure (RT-F) and non-failure (RT-NF) on muscle mass, strength and activation of trained individuals. We also compared the effects of these protocols on muscle architecture parameters. A within-subjects design was used in which 14 participants had one leg randomly assigned to RT-F and the other to RT-NF. Each leg was trained 2 days per week for 10 weeks. Vastus lateralis (VL) muscle cross-sectional area (CSA), pennation angle (PA), fascicle length (FL) and 1-repetition maximum (1-RM) were assessed at baseline (Pre) and after 20 sessions (Post). The electromyographic signal (EMG) was assessed after the training period. RT-F and RT-NF protocols showed significant and similar increases in CSA (RT-F: 13.5% and RT-NF: 18.1%; P < 0.0001), PA (RT-F: 13.7% and RT-NF: 14.4%; P < 0.0001) and FL (RT-F: 11.8% and RT-NF: 8.6%; P < 0.0001). All protocols showed significant and similar increases in leg press (RT-F: 22.3% and RT-NF: 26.7%; P < 0.0001) and leg extension (RT-F: 33.3%, P < 0.0001 and RT-NF: 33.7%; P < 0.0001) 1-RM loads. No significant differences in EMG amplitude were detected between protocols (P > 0.05). In conclusion, RT-F and RT-NF are similarly effective in promoting increases in muscle mass, PA, FL, strength and activation.