Joao Guilherme Almeida Bergamasco

A large, abrupt increase in weekly resistance training volume (+120% relative to habitual training) did not enhance muscle hypertrophy compared with a modest increase (+20%) in resistance-trained individuals. We found no evidence that the larger volume progression attenuated adaptation under the present experimental conditions. Acute and chronic molecular responses likewise did not differ significantly between protocols.

Skeletal muscle hypertrophy results from the integrated regulation of anabolic and proteolytic processes in response to mechanical loading. Although increases in resistance training (RT) volume are used to increase mechanical stress, it remains uncertain whether large and abrupt volume progressions could exceed muscle adaptive capacity by disrupting the balance between anabolic and catabolic signaling. The present study investigated whether a large increase in weekly RT volume (+120%) leads to impaired hypertrophic outcomes and intracellular regulatory responses compared with a modest increase (+20%). Twenty-five resistance-trained men and women (18–35 years old) completed an 8-week randomized, single-blind, within-subject unilateral intervention. Each participant trained both legs twice weekly, with one leg assigned to the large (VOL120) and the contralateral leg to the modest (VOL20) weekly volume progressions relative to habitual training volume. Vastus lateralis muscle cross-sectional area (mCSA) was assessed by ultrasonography before and after training. Muscle biopsies were obtained at baseline, post-intervention, and 24 h after the last session to quantify muscle fiber cross-sectional area (fCSA), satellite cell myonuclear content, and anabolic/catabolic signaling markers. Both protocols induced increases in mCSA over time ( p <0.001), with no protocol vs. time interaction. No significant effects were observed for fCSA nor satellite cell number or myonuclear content. Additionally, molecular responses related to translational regulation and protein degradation were largely similar between protocols. Collectively, these data indicate that a large, abrupt increase in weekly set volume does not impair hypertrophic adaptations or meaningfully alter the anabolic–catabolic signaling profile in resistance-trained individuals.

This is the first study to evaluate acute and chronic resistance training-induced changes in skeletal muscle estrogen receptor alpha (ERα) signaling and satellite cell (SC) dynamics in women and men. Although ERα content differed between sexes and SC increased with training, ERα markers were not consistently linked to muscle hypertrophy, particularly in women. These findings challenge the presumed role of ERα in hypertrophic adaptation and provide new insights into sex-specific mechanisms of muscle remodeling.

Resistance training (RT) volume is recognized as a key variable driving skeletal muscle hypertrophy. Meta-analyses have supported a positive dose–response relationship, with greater volumes resulting in more pronounced hypertrophic adaptations. However, more recent studies conducted in trained individuals have reported conflicting findings, raising the question of whether a saturation point, defined here as a theoretical threshold beyond which additional training volume no longer yields benefits, might exist, or whether the inconsistencies are better explained by methodological limitations and individual variability. In this narrative review, we explore physiological and methodological factors that may explain such discrepancies. Mechanistically, higher RT volumes are associated with greater anabolic signaling, myofibrillar protein synthesis, ribosomal biogenesis, and satellite cell activation, although these results are not universal. Moreover, excessive training volumes may elevate muscle protein breakdown via activation of catabolic pathways. Methodological factors such as the muscle group and exercises selected, lack of control for prior training volume, overestimation of effect sizes in power calculations, and between-subject variability challenge the interpretation of dose–response relationships. Collectively, these physiological mechanisms and methodological challenges highlight the complexity of establishing a clear and consistent relationship between RT volume and muscle hypertrophy. Expanding our knowledge of the RT dose–response relationship will require rigorous experimental designs, integration of molecular and morphological outcomes, and a greater focus on inter-individual variability. These elements may help clarify whether a true saturation point in RT volume exists for anabolic signaling and muscle hypertrophy.

Purpose We aimed to compare individual hypertrophic responses to resistance training in which overload progressed either by adjusting the load (LOADProg) or by increasing the number of repetitions (REPSProg). Furthermore, we investigated whether greater responsiveness to one protocol was associated with chronic changes in myonuclei and satellite cells, proteolysis and extracellular matrix (ECM) remodeling biomarkers. Methods Thirty-seven untrained participants had their legs randomized into LOADProg and REPSProg and underwent 10 weeks of training. Muscle cross-sectional area (mCSA) ultrasound and muscle biopsies were performed pre- and post-training. Based on mCSA changes between protocols, we applied a criterion of 2 typical errors (5.7%) to create 4 clusters. Results Twelve participants (~ 34%) showed greater mCSA increases after REPSProg (14.2 ± 7.6%) than LOADProg (3.4 ± 8.7%, p = 0.004). Seven participants (~ 19%) responded better to LOADProg (21.5 ± 7.5% vs. 12 ± 7.5%, p = 0.041). Thirteen participants (~ 35%) showed no differences between protocols (p = 0.852). Five participants were nonresponders (mCSA changes smaller than the 5.7% threshold) for both protocols. There were no significant differences (p > 0.05) in myonuclear content, proteolysis, or ECM remodeling markers within any of the clusters. However, for those who responded better to REPSProg, this protocol promoted greater satellite cell changes (108.6 ± 77.0%) than LOADProg (48.9 ± 63.1%, p = 0.015). Conclusion Our findings suggest that overload progression models may influence individual responsiveness to RT-induced muscle hypertrophy. Additionally, progression through increased repetitions was associated with a chronic addition of satellite cells. However, responsiveness was not explained by chronic changes in myonuclei, proteolysis or ECM remodeling biomarkers. Trial registration This study is registered in the Brazilian Registry of Clinical Trials (RBR-57v9mrb).

We aimed to compare individual hypertrophic responses to high-load resistance training (HL-RT) or high-load with blood flow restriction (HL-BFR). Furthermore, we investigated whether greater responsiveness to one of the protocols could be explained by acute changes in blood deoxyhemoglobin concentration (HHb) and total hemoglobin concentration (tHb) (proxy markers of metabolic stress). Ten untrained participants had their legs randomized into both HL-RT and HL-BFR and underwent 10 weeks of training. Muscle cross-sectional area (mCSA) was measured at baseline and post training, while HHb and tHb during the final session. Using a threshold of 2 × typical errors (3.24%) to compare protocols, five participants showed greater mCSA increases after HL-RT (16.44 ± 7.90%) compared to HL-BFR (10.74 ± 7.12%, p = 0.0054) and five did not respond better to HL-RT (8.95 ± 10.83%) compared to HL-BFR (13.33 ± 8.59%) (p = 0.3105). Additionally, HL-RT induced lower HHb (5855.78 ± 12905.99; p = 0.0101) and tHb (-43169.70 ± 37793.17; p = 0.0030) AUC values compared to HL-BFR (HHb: 39254.80 ± 27020.15; tHb: 46309.40 ± 31613.97). In conclusion, despite the higher levels of metabolic stress markers, most participants did not present greater muscle hypertrophy by combining blood flow restriction with HL-RT.

We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men ( n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study ( n = 7) and a study involving 2 weeks of leg immobilization ( n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHC _Total ) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHC _Total fragmentation 24 h post‐RE (+65% and +36%, P  < 0.001); however, the last RE bout response was attenuated compared to the first bout ( P = 0.045). Although cycling exercise did not alter MyHC _Total fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHC _Total fragmentation (∼108%, P  < 0.001). Mechanistic C ₂ C ₁₂ myotube experiments indicated that MyHC _Total fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease‐associated muscle atrophy affect these outcomes is needed. Highlights: What is the central question of this study? How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation. What is the main finding and its importance? This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.

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.