Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.

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.

Resistance training diminishes mitochondrial adaptations to subsequent endurance training in healthy untrained men.

We investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty-five young adults were divided into an RT+ET group (n = 13), which underwent 7 weeks of RT followed by 7 weeks of ET, and an ET-only group (n = 12), which performed 7 weeks of ET. Body composition, endurance performance and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, after RT for RT+ET and baseline for ET) and after ET (T3). Immunohistochemistry was performed to determine fibre cross-sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodelling. Citrate synthase activity and markers of ribosome content were also investigated. RT improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (P < 0.050). In response to ET, both groups similarly decreased body fat percentage (P < 0.0001) and improved endurance performance (e.g. V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ , and speed at which the onset of blood lactate accumulation occurred, P < 0.0001). Levels of mitochondrial complexes I-IV in the ET-only group increased 32-66%, while those in the RT+ET group increased 1-11% (time, P < 0.050). Additionally, mixed fibre relative mitochondrial content increased 15% in the ET-only group but decreased 13% in the RT+ET group (interaction, P = 0.043). In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET. KEY POINTS: Resistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function. Although several concurrent training studies are available, in this study we investigated the effects of performing a period of resistance training on the performance and molecular adaptations to subsequent endurance training. Prior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but this effect may have been a result of detraining from resistance training.

Proteolytic markers associated with a gain and loss of leg muscle mass with resistance training followed by high-intensity interval training.

We recently reported that vastus lateralis (VL) cross-sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high-intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college-aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P < 0.05). 20S proteasome core protein abundance increased at POST versus PRE (P = 0.031) and MID (P = 0.049). 20S proteasome activity, and protein levels for calpain-2 and Beclin-1 increased at MID and POST versus PRE (P < 0.05). Ubiquitinated proteins showed model significance (P = 0.019) with non-significant increases at MID and POST (P > 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin-like growth factor 1; IGF1) followed by a subsequent AMP-activated protein kinase activator (5-aminoimidazole-4-carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1-treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1-treated versus I+A myotubes (P < 0.001). In summary, the loss in RT-induced VL CSA with HIIT coincided with increases in several proteolytic markers, and sustained proteolysis may have driven this response. Moreover, while not measured in humans, we interpret our in vitro data to suggest that (unlike RT) HIIT does not stimulate MPS. NEW FINDINGS: What is the central question of this study? Determining if HIIT-induced reductions in muscle hypertrophy following a period of resistance training coincided with increases in proteolytic markers. What is the main finding and its importance? Several proteolytic markers were elevated during the HIIT training period implying that increases in muscle proteolysis may have played a role in HIIT-induced reductions in muscle hypertrophy.

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.

Time Course of Proteolysis Biomarker Responses to Resistance, High-Intensity Interval, and Concurrent Exercise Bouts.

ABSTRACT: Godwin, JS, Telles, GD, Vechin, FC, Conceição, MS, Ugrinowitsch, C, Roberts, MD, and Libardi, CA. Time course of proteolysis biomarker responses to resistance, high-intensity interval, and concurrent exercise bouts. J Strength Cond Res 37(12): 2326-2332, 2023-Concurrent exercise (CE) combines resistance exercise (RE) and high-intensity interval exercise (HIIE) in the same training routine, eliciting hypertrophy, strength, and cardiovascular benefits over time. Some studies suggest that CE training may hamper muscle hypertrophy and strength adaptations compared with RE training alone. However, the underlying mechanisms related to protein breakdown are not well understood. The purpose of this study was to examine how a bout of RE, HIIE, or CE affected ubiquitin-proteasome and calpain activity and the expression of a few associated genes, markers of skeletal muscle proteolysis. Nine untrained male subjects completed 1 bout of RE (4 sets of 8-12 reps), HIIE (12 × 1 minute sprints at V̇ o2 peak minimum velocity), and CE (RE followed by HIIE), in a crossover design, separated by 1-week washout periods. Muscle biopsies were obtained from the vastus lateralis before (Pre), immediately post, 4 hours (4 hours), and 8 hours (8 hours) after exercise. FBXO32 mRNA expression increased immediately after exercise (main time effect; p < 0.05), and RE and CE presented significant overall values compared with HIIE ( p < 0.05). There was a marginal time effect for calpain-2 mRNA expression ( p < 0.05), with no differences between time points ( p > 0.05). No significant changes occurred in TRIM63/MuRF-1 and FOXO3 mRNA expression, or 20S proteasome or calpain activities ( p > 0.05). In conclusion, our findings suggest that 1 bout of CE does not promote greater changes in markers of skeletal muscle proteolysis compared with 1 bout of RE or HIIE.

Changes in vastus lateralis fibre cross-sectional area, pennation angle and fascicle length do not predict changes in muscle cross-sectional area.

NEW FINDINGS: What is the central question of this study? Do changes in myofibre cross-sectional area, pennation angle and fascicle length predict vastus lateralis whole-muscle cross-sectional area changes following resistance training? What is the main finding and its importance? Changes in vastus lateralis mean myofibre cross-sectional area, fascicle length and pennation angle following a period of resistance training did not collectively predict changes in whole-muscle cross-sectional area. Despite the limited sample size in this study, these data reiterate that it remains difficult to generalize the morphological adaptations that predominantly drive tissue-level vastus lateralis muscle hypertrophy. ABSTRACT: Myofibre hypertrophy during resistance training (RT) poorly associates with tissue-level surrogates of hypertrophy. However, it is underappreciated that, in pennate muscle, changes in myofibre cross-sectional area (fCSA), fascicle length (Lf ) and pennation angle (PA) likely coordinate changes in whole-muscle cross-sectional area (mCSA). Therefore, we determined if changes in fCSA, PA and Lf predicted vastus lateralis (VL) mCSA changes following RT. Thirteen untrained college-aged males (23 ± 4 years old, 25.4 ± 5.2 kg/m2 ) completed 7 weeks of full-body RT (twice weekly). Right leg VL ultrasound images and biopsies were obtained prior to (PRE) and 72 h following (POST) the last training bout. Regression was used to assess if training-induced changes in mean fCSA, PA and Lf predicted VL mCSA changes. Correlations were also performed between PRE-to-POST changes in obtained variables. Mean fCSA (+18%), PA (+8%) and mCSA (+22%) increased following RT (P < 0.05), but not Lf (0.1%, P = 0.772). Changes in fCSA, Lf and PA did not collectively predict changes in mCSA (R2 = 0.282, adjusted R2 = 0.013, F3,8  = 1.050, P = 0.422). Moderate negative correlations existed for percentage changes in PA and Lf (r = -0.548, P = 0.052) and changes in fCSA and Lf (r = -0.649, P = 0.022), and all other associations were weak (|r| < 0.500). Although increases in mean fCSA, PA and VL mCSA were observed, inter-individual responses for each variable and limitations for each technique make it difficult to generalize the morphological adaptations that predominantly drive tissue-level VL muscle hypertrophy. However, the small subject pool is a significant limitation, and more research in this area is needed.

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.

Individual Muscle Hypertrophy and Strength Responses to High vs. Low Resistance Training Frequencies.

Damas, F, Barcelos, C, Nóbrega, SR, Ugrinowitsch, C, Lixandrão, ME, Santos, LMEd, Conceição, MS, Vechin, FC, and Libardi, CA. Individual muscle hypertrophy and strength responses to high vs. low resistance training frequencies. J Strength Cond Res 33(4): 897-901, 2019-The aim of this short communication was to compare the individual muscle mass and strength gains with high (HF) vs. low (LF) resistance training (RT) frequencies using data from our previous study. We used a within-subject design in which 20 subjects had one leg randomly assigned to HF (5× per week) and the other to LF (2 or 3× per week). Muscle cross-sectional area and 1 repetition maximum were assessed at baseline and after 8 weeks of RT. HF showed a higher 8-week accumulated total training volume (TTV) (p < 0.0001) compared with LF. Muscle cross-sectional area and 1 repetition maximum values increased significantly and similarly for HF and LF protocols (p > 0.05). This short communication highlights that some individuals showed greater muscle mass and strength gains after HF (31.6 and 26.3% of individuals, respectively), other had greater gains with LF (36.8 and 15.8% of individuals, respectively), and even others showed similar responses between HF and LF, regardless of the consequent higher or lower TTV resulted from HF and LF, respectively. Importantly, individual manipulation of RT frequency can improve the intrasubject responsiveness to training, but the effect is limited to each individual's capacity to respond to RT. Finally, individual response to different frequencies and resulted TTV does not necessarily agree between muscle hypertrophy and strength gains.

The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis.

Resistance training (RT)-induced skeletal muscle hypertrophy is a highly intricate process. Despite substantial advances, we are far from understanding exactly how muscle hypertrophy develops during RT. The aim of the present review is to discuss new insights related to the role of skeletal muscle damage and muscle protein synthesis (MPS) in mediating RT-induced hypertrophy. Specifically, the thesis that in the early phase of RT (≤ 4 previous RT sessions) increases in muscle cross-sectional area are mostly attributable to muscle damage-induced muscle swelling; then (after ~ 10 sessions), a modest magnitude of muscle hypertrophy ensues; but only during a latter phase of RT (after ~ 18 sessions) is true muscle hypertrophy observed. We argue that the initial increases in MPS post-RT are likely directed to muscle repair and remodelling due to damage, and do not correlate with eventual muscle hypertrophy induced by several RT weeks. Increases in MPS post-RT session only contribute to muscle hypertrophy after a progressive attenuation of muscle damage, and even more significantly when damage is minimal. Furthermore, RT protocols that do not promote significant muscle damage still induce similar muscle hypertrophy and strength gains compared to conditions that do promote initial muscle damage. Thus, we conclude that muscle damage is not the process that mediates or potentiates RT-induced muscle hypertrophy.

Resistance training in young men induces muscle transcriptome-wide changes associated with muscle structure and metabolism refining the response to exercise-induced stress.

BACKGROUND: Gene expression is an important process underpinning the acute and chronic adaptive response to resistance exercise (RE) training. PURPOSE: To investigate the effect of training status on vastus lateralis muscle global transcriptome at rest and following acute RE. METHODS: Muscle biopsies of nine young men (age: 26(2) years; body mass: 69(9) kg; height 172(6) cm) who undertook RE training for 10 weeks were collected pre and 24 h post-RE in the untrained (W1) and trained (W10) states and analysed using microarray. Tests of differential expression were conducted for rested and after RE contrasts in both training states. To control for false discovery rate (FDR), multiple testing correction was performed at a cut-off of FDR < 0.05. RESULTS: Unaccustomed RE (at W1) upregulated muscle gene transcripts related to stress (e.g., heat shock proteins), damage and inflammation, structural remodelling, protein turnover and increased translational capacity. Trained muscles (at W10) showed changes in the transcriptome signature regarding the regulation of energy metabolism, favouring a more oxidative one, upregulated antioxidant- and immune-related genes/terms, and gene transcripts related to the cytoskeleton and extracellular matrix, muscle contraction, development and growth. CONCLUSIONS: These results highlight that chronic repetition of RE changes muscle transcriptome response towards a more refined response to RE-induced stress.

Effect of Resistance Training to Muscle Failure vs. Volitional Interruption at High- and Low-Intensities on Muscle Mass and Strength.

Nóbrega, SR, Ugrinowitsch, C, Pintanel, L, Barcelos, C, and Libardi, CA. Effect of resistance training to muscle failure vs. volitional interruption at high- and low-intensities on muscle mass and strength. J Strength Cond Res 32(1): 162-169, 2018-The purpose of this study was to investigate the effects of resistance training (RT) at high- and low-intensities performed to muscle failure or volitional interruption on muscle strength, cross-sectional area (CSA), pennation angle (PA), and muscle activation. Thirty-two untrained men participated in the study. Each leg was allocated in 1 of 4 unilateral RT protocols: RT to failure at high and low intensities, and RT to volitional interruption (repetitions performed to the point in which participants voluntarily interrupted the exercise) at high (HIRT-V) and low (LIRT-V) intensities. Muscle strength (1 repetition maximum [1RM]), CSA, PA, and muscle activation by amplitude of the electromyography (EMG) signal were assessed before (Pre), after 6 (6W), and 12 (12W) weeks. 1RM increased similarly after 6W (range: 15.8-18.9%, effective size [ES]: 0.41-0.58) and 12W (range: 25.6-33.6%, ES: 0.64-0.98) for all protocols. All protocols were similarly effective in increasing CSA after 6W (range: 3.0-4.6%, ES: 0.10-0.24) and 12W (range: 6.1-7.5%, ES: 0.22-0.26). PA increased after 6W (∼3.5) and 12W (∼9%; main time effect, p < 0.0001), with no differences between protocols. EMG values were significantly higher for the high-intensity protocols at all times (main intensity effect, p < 0.0001). In conclusion, both HIRT-V and LIRT-V are equally effective in increasing muscle mass, strength, and PA when compared with RT performed to muscle failure.

Acute low-intensity cycling with blood-flow restriction has no effect on metabolic signaling in human skeletal muscle compared to traditional exercise.

PURPOSE: Autophagy is an intracellular degradative system sensitive to hypoxia and exercise-induced perturbations to cellular bioenergetics. We determined the effects of low-intensity endurance-based exercise performed with blood-flow restriction (BFR) on cell signaling adaptive responses regulating autophagy and substrate metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, nine young, healthy but physically inactive males completed three experimental trials separated by 1 week of recovery consisting of either a resistance exercise bout (REX: 4 × 10 leg press repetitions, 70% 1-RM), endurance exercise (END: 30 min cycling, 70% VO2peak), or low-intensity cycling with BFR (15 min, 40% VO2peak). A resting muscle biopsy was obtained from the vastus lateralis 2 weeks prior to the first exercise trial and 3 h after each exercise bout. RESULTS: END increased ULK1Ser757 phosphorylation above rest and BFR (~37 to 51%, P < 0.05). Following REX, there were significant elevations compared to rest (~348%) and BFR (~973%) for p38γ MAPKThr180/Tyr182 phosphorylation (P < 0.05). Parkin content was lower following BFR cycling compared to REX (~20%, P < 0.05). There were no exercise-induced changes in select markers of autophagy following BFR. Genes implicated in substrate metabolism (HK2 and PDK4) were increased above rest (~143 to 338%) and BFR cycling (~212 to 517%) with END (P < 0.001). CONCLUSION: A single bout of low-intensity cycling with BFR is insufficient to induce intracellular "stress" responses (e.g., high rates of substrate turnover and local hypoxia) necessary to activate skeletal muscle autophagy signaling.

Metabolic time-course response after resistance exercise: A metabolomics approach.

This study analysed the time course of the global metabolic acute response after resistance exercise (RE), with the use of proton nuclear magnetic resonance (1H NMR) spectroscopy. Ten young healthy males performed 4 sets of 10 repetitions at 70% of one-repetition maximum in the leg press and knee extension exercises and had the serum metabolome assessed at 5, 15, 30 and 60 min post-RE. Measurements were also performed 1 h earlier and immediately before the exercises, as an attempt to characterise each participant's serum metabolome at rest. One-way ANOVA was applied and the significance level was set at P ≤ 0.05. RE promoted an increase in 2-hydroxybutyrate, 2-oxoisocaproate, 3-hydroxyisobutyrate, alanine, hypoxanthine, lactate, pyruvate and succinate concentrations. However, isoleucine, leucine, lysine, ornithine and valine had their concentrations decreased post-RE compared with at rest. This is the first study to show significant changes in serum concentration of metabolites such as 2-oxoisocaproate, 2-hydroxybutyrate, 3-hydroxyisobutyrate, lysine, hypoxanthine and pyruvate post-RE, attesting metabolomics as an interesting approach to advance in the understanding of global RE-induced metabolic changes. Moreover, the present data could influence the time point of blood collection in the future studies that aims to investigate metabolism and exercise.

Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage.

KEY POINTS: Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage. ABSTRACT: Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P < 0.03) than at T2 and T3 (similar values between T2 and T3). Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P < 0.04) with muscle hypertrophy. Initial MyoPS response post-RE in an RT programme is not directed to support muscle hypertrophy, coinciding with the greatest muscle damage. However, integrated MyoPS is quickly 'refined' by 3 weeks of RT, and is related to muscle hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent changes in MyoPS post-RE in RT, which coincides with progressive attenuation of muscle damage.

Early resistance training-induced increases in muscle cross-sectional area are concomitant with edema-induced muscle swelling.

PURPOSE: It has been proposed that skeletal muscle shows signs of resistance training (RT)-induced muscle hypertrophy much earlier (i.e., ~3-4 weeks of RT) than previously thought. We determined if early increases in whole muscle cross-sectional area (CSA) during a period of RT were concomitant with edematous muscle swelling and thus not completely attributable to hypertrophy. METHODS: We analyzed vastus lateralis muscle ultrasound CSA images and their respective echo intensities (CSA-USecho) at the beginning (T1), in the 3rd week of RT (T2) and at the end (T3) of a 10-week RT period in ten untrained young men. Functional parameters [training volume (TV = load × reps × sets) and maximal voluntary contraction (MVC)] and muscle damage markers (myoglobin and interleukin-6) were also assessed. RESULT: Muscle CSA increased significantly at T2 (~2.7%) and T3 (~10.4%) versus T1. Similarly, CSA-USecho increased at T2 (~17.2%) and T3 (~13.7%). However, when CSA-USecho was normalized to the increase in muscle CSA, only T2 showed a significantly higher USecho versus T1. Additionally, TV increased at T2 and T3 versus T1, but MVC increased only at T3. Myoglobin and Interleukin-6 were elevated at T2 versus T1, and myoglobin was also higher at T2 versus T3. CONCLUSION: We propose that early RT-induced increases in muscle CSA in untrained young individuals are not purely hypertrophy, since there is concomitant edema-induced muscle swelling, probably due to muscle damage, which may account for a large proportion of the increase. Therefore, muscle CSA increases (particularly early in an RT program) should not be labeled as hypertrophy without some concomitant measure of muscle edema/damage.

Time Course of Resistance Training-Induced Muscle Hypertrophy in the Elderly.

Extended periods of resistance training (RT) induce muscle hypertrophy. Nevertheless, to date, no study has investigated the time window necessary to observe significant changes in muscle cross-sectional area (CSA) in older adults. Therefore, this study investigated the time course of muscle hypertrophy after 10 weeks (20 sessions) of RT in the elderly. Fourteen healthy older subjects were randomly allocated in either the RT (n: 6) or control group (n: 8). The RT was composed of 4 sets × 10 repetitions (70-80% 1 repetition maximum [1RM]) in a leg press machine. The time course of vastus lateralis muscle hypertrophy (CSA) was assessed on a weekly basis by mode-B ultrasonography. Leg press muscle strength was assessed by dynamic 1RM test. Our results demonstrated that the RT group increased leg press 1RM by 42% (p ≤ 0.05) after 10 weeks of training. Significant increases in vastus lateralis muscle CSA were observed only after 18 sessions of training (9 weeks; p ≤ 0.05; 7.1%). In conclusion, our training protocol promoted muscle mass accrual in older subjects, and this was only observable after 18 sessions of RT (9 weeks).

Effects of exercise intensity and occlusion pressure after 12 weeks of resistance training with blood-flow restriction.

PURPOSE: We compared the effects of different protocols of blood-flow restriction training (BFRT) with different occlusion pressures and/or exercise intensities on muscle mass and strength. We also compared BFRT protocols with conventional high-intensity resistance training (RT). METHODS: Twenty-six subjects had each leg allocated to two of five protocols. BFRT protocols were performed at either 20 or 40 % 1-RM with either 40 or 80 % occlusion pressure: BFRT20/40, BFRT20/80, BFRT40/40, and BFRT40/80. Conventional RT was performed at 80 % 1-RM (RT80) without blood-flow restriction. Maximum dynamic strength (1-RM) and quadriceps cross-sectional area (CSA) were assessed at baseline and after 12 weeks. RESULTS: Regarding muscle mass, increasing occlusion pressure was effective only at very low intensity (BFRT20/40 0.78 % vs. BFRT20/80 3.22 %). No additional increase was observed at higher intensities (BFRT40/40 4.45 % vs. BFRT40/80 5.30 %), with no difference between the latter protocols and RT80 (5.90 %). Exercise intensity played a role in CSA when comparing groups with similar occlusion pressure. Muscle strength was similarly increased among BFRT groups (~12.10 %) but to a lesser extent than RT80 (21.60 %). CONCLUSION: In conclusion, BFRT protocols benefit from higher occlusion pressure (80 %) when exercising at very low intensities. Conversely, occlusion pressure seems secondary to exercise intensity in more intense (40 % 1-RM) BFRT protocols. Finally, when considering muscle strength, BFRT protocols seem less effective than high-intensity RT.