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Physiological Reviews Oct 2023Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of... (Review)
Review
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.
Topics: Humans; Animals; Dogs; Muscle, Skeletal; Signal Transduction; Mechanistic Target of Rapamycin Complex 1; Protein Biosynthesis; Hypertrophy; Mammals
PubMed: 37382939
DOI: 10.1152/physrev.00039.2022 -
British Journal of Sports Medicine Sep 2023To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy.
DATA SOURCES
MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022.
ELIGIBILITY CRITERIA
Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included.
ANALYSES
Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis.
RESULTS
The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (>80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust.
CONCLUSION
All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets.
PROSPERO REGISTRATION NUMBER
CRD42021259663 and CRD42021258902.
Topics: Humans; Adult; Female; Resistance Training; Bayes Theorem; Network Meta-Analysis; Muscle, Skeletal; Muscle Strength; Hypertrophy; Prescriptions
PubMed: 37414459
DOI: 10.1136/bjsports-2023-106807 -
Current Opinion in Clinical Nutrition... Jul 2023Highlight contemporary evidence examining the effects of carbohydrate restriction on the intracellular regulation of muscle mass and anaerobic performance. (Review)
Review
PURPOSE OF REVIEW
Highlight contemporary evidence examining the effects of carbohydrate restriction on the intracellular regulation of muscle mass and anaerobic performance.
RECENT FINDINGS
Low carbohydrate diets increase fat oxidation and decrease fat mass. Emerging evidence suggests that dietary carbohydrate restriction increases protein oxidation, thereby limiting essential amino acid availability necessary to stimulate optimal muscle protein synthesis and promote muscle recovery. Low carbohydrate feeding for 24 h increases branched-chain amino acid (BCAA) oxidation and reduces myogenic regulator factor transcription compared to mixed-macronutrient feeding. When carbohydrate restriction is maintained for 8 to 12 weeks, the alterations in anabolic signaling, protein synthesis, and myogenesis likely contribute to limited hypertrophic responses to resistance training. The blunted hypertrophic response to resistance training when carbohydrate availability is low does not affect muscle strength, whereas persistently low muscle glycogen does impair anaerobic output during high-intensity sprint and time to exhaustion tests.
SUMMARY
Dietary carbohydrate restriction increases BCAA oxidation and impairs muscle hypertrophy and anaerobic performance, suggesting athletes who need to perform high-intensity exercise should consider avoiding dietary strategies that restrict carbohydrate.
Topics: Humans; Physical Endurance; Anaerobiosis; Dietary Carbohydrates; Diet, Carbohydrate-Restricted; Amino Acids, Branched-Chain; Hypertrophy; Muscle, Skeletal
PubMed: 37057671
DOI: 10.1097/MCO.0000000000000934 -
Nature Reviews. Cardiology Dec 2023Cardiac metabolism is vital for heart function. Given that cardiac contraction requires a continuous supply of ATP in large quantities, the role of fuel metabolism in... (Review)
Review
Cardiac metabolism is vital for heart function. Given that cardiac contraction requires a continuous supply of ATP in large quantities, the role of fuel metabolism in the heart has been mostly considered from the perspective of energy production. However, the consequence of metabolic remodelling in the failing heart is not limited to a compromised energy supply. The rewired metabolic network generates metabolites that can directly regulate signalling cascades, protein function, gene transcription and epigenetic modifications, thereby affecting the overall stress response of the heart. In addition, metabolic changes in both cardiomyocytes and non-cardiomyocytes contribute to the development of cardiac pathologies. In this Review, we first summarize how energy metabolism is altered in cardiac hypertrophy and heart failure of different aetiologies, followed by a discussion of emerging concepts in cardiac metabolic remodelling, that is, the non-energy-generating function of metabolism. We highlight challenges and open questions in these areas and finish with a brief perspective on how mechanistic research can be translated into therapies for heart failure.
Topics: Humans; Cardiomegaly; Heart Failure; Myocytes, Cardiac; Energy Metabolism; Signal Transduction; Myocardium
PubMed: 37237146
DOI: 10.1038/s41569-023-00887-x -
Journal of Strength and Conditioning... Sep 2023Kassiano, W, Costa, B, Kunevaliki, G, Soares, D, Zacarias, G, Manske, I, Takaki, Y, Ruggiero, MF, Stavinski, N, Francsuel, J, Tricoli, I, Carneiro, MAS, and Cyrino, ES.... (Randomized Controlled Trial)
Randomized Controlled Trial
Kassiano, W, Costa, B, Kunevaliki, G, Soares, D, Zacarias, G, Manske, I, Takaki, Y, Ruggiero, MF, Stavinski, N, Francsuel, J, Tricoli, I, Carneiro, MAS, and Cyrino, ES. Greater gastrocnemius muscle hypertrophy after partial range of motion training performed at long muscle lengths. J Strength Cond Res 37(9): 1746-1753, 2023-Whether there is an optimal range of motion (ROM) to induce muscle hypertrophy remains elusive, especially for gastrocnemius. This study aimed to compare the changes in gastrocnemius muscle thickness between calf raise exercise performed with full ROM (FULL ROM ), partial ROM performed in the initial (INITIAL ROM ), and final (FINAL ROM ) portions of the ROM. Forty-two young women performed a calf training program for 8 weeks, 3 days·week -1 , with differences in the calf raise ROM configuration. The calf raise exercise was performed in a pin-loaded, horizontal, leg-press machine, in 3 sets of 15-20 repetition maximum. The subjects were randomly assigned to 1 of the 3 groups: FULL ROM (ankle: -25° to +25°), INITIAL ROM (ankle: -25° to 0°), and FINAL ROM (ankle: 0° to +25°), where 0° was defined as an angle of 90° of the foot with the tibia. The muscle thickness measurements of medial and lateral gastrocnemius were taken by means of B-mode ultrasound. INITIAL ROM elicited greater medial gastrocnemius increases than FULL ROM and FINAL ROM (INITIAL ROM = +15.2% vs. FULL ROM = +6.7% and FINAL ROM = +3.4%; p ≤ 0.009). Furthermore, INITIAL ROM elicited greater lateral gastrocnemius increases than FINAL ROM (INITIAL ROM = +14.9% vs. FINAL ROM = +6.2%; p < 0.024) but did not significantly differ from FULL ROM (FULL ROM = +7.3%; p = 0.060). The current results suggest that calf training performed at longer muscle lengths may optimize gastrocnemius muscle hypertrophy in young women. Therefore, when prescribing hypertrophy-oriented training, the inclusion of the calf raise exercise performed with partial ROM in the initial portion of the excursion should be considered.
Topics: Humans; Female; Muscle, Skeletal; Leg; Ankle; Range of Motion, Articular; Hypertrophy; Muscle Strength
PubMed: 37015016
DOI: 10.1519/JSC.0000000000004460 -
European Journal of Sport Science Jul 2023The biarticular triceps brachii long head (TB) is lengthened more in the overhead than neutral arm position. We compared triceps brachii hypertrophy after elbow...
The biarticular triceps brachii long head (TB) is lengthened more in the overhead than neutral arm position. We compared triceps brachii hypertrophy after elbow extension training performed in the overhead vs. neutral arm position. Using a cable machine, 21 adults conducted elbow extensions (90-0°) with one arm in the overhead (Overhead-Arm) and the other arm in the neutral (Neutral-Arm) position at 70% one-repetition maximum (1RM), 10 reps/set, 5 sets/session, 2 sessions/week for 12 weeks. Training load was gradually increased (+5% 1RM/session) when the preceding session was completed without repetition failure. 1RM of the assigned condition and MRI-measured muscle volume of the TB, monoarticular lateral and medial heads (TB), and whole triceps brachii (Whole-TB) were assessed pre- and post-training. Training load and 1RM increased in both arms similarly (+62-71% at post, = 0.285), while their absolute values/weights were always lower in Overhead-Arm (-34-39%, < 0.001). Changes in muscle volume in Overhead-Arm compared to Neutral-Arm were 1.5-fold greater for the TB (+28.5% vs. +19.6%, Cohen's = 0.61, < 0.001), 1.4-fold greater for the TB (+14.6% vs. +10.5%, = 0.39, = 0.002), and 1.4-fold greater for the Whole-TB (+19.9% vs. +13.9%, = 0.54, < 0.001). In conclusion, triceps brachii hypertrophy was substantially greater after elbow extension training performed in the overhead versus neutral arm position, even with lower absolute loads used during the training.Growing evidence suggests that resistance training at long muscle lengths promotes muscle hypertrophy, but its practical applications are yet to be explored.Triceps brachii muscle hypertrophy was substantially greater after cable elbow extension training performed in the overhead than neutral arm position, particularly in the biarticular triceps brachii long head, even with lower absolute loads lifted (i.e. lower mechanical stress to muscles/joints).Cable elbow extension training should be performed in the overhead rather than neutral arm position if one aims to maximise muscle hypertrophy of the triceps brachii or to prevent atrophy of this muscle.
Topics: Adult; Humans; Elbow; Elbow Joint; Muscle, Skeletal; Resistance Training; Hypertrophy
PubMed: 35819335
DOI: 10.1080/17461391.2022.2100279 -
Signal Transduction and Targeted Therapy Oct 2023Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction (MI) heart failure (HF). Here, we report a novel small molecule...
Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction (MI) heart failure (HF). Here, we report a novel small molecule HHQ16, an optimized derivative of astragaloside IV, which effectively reversed infarction-induced myocardial remodeling and improved cardiac function by directly acting on the cardiomyocyte to reverse hypertrophy. The effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affiliated transcript lnc9456 in the heart. While minimally expressed in normal mouse heart, lnc9456 was dramatically upregulated in the heart subjected to left anterior descending coronary artery ligation (LADL) and in cardiomyocytes subjected to hypertrophic stimulation. The critical role of lnc9456 in cardiomyocyte hypertrophy was confirmed by specific overexpression and knockout in vitro. A physical interaction between lnc9456 and G3BP2 increased NF-κB nuclear translocation, triggering hypertrophy-related cascades. HHQ16 physically bound to lnc9456 with a high-affinity and induced its degradation. Cardiomyocyte-specific lnc9456 overexpression induced, but knockout prevented LADL-induced, cardiac hypertrophy and dysfunction. HHQ16 reversed the effect of lnc9456 overexpression while lost its protective role when lnc9456 was deleted, further confirming lnc9456 as the bona fide target of HHQ16. We further identified the human ortholog of lnc9456, also an Egr2-affiliated transcript, lnc4012. Similarly, lnc4012 was significantly upregulated in hypertrophied failing hearts of patients with dilated cardiomyopathy. HHQ16 also specifically bound to lnc4012 and caused its degradation and antagonized its hypertrophic effects. Targeted degradation of pathological increased lnc4012/lnc9456 by small molecules might serve as a novel promising strategy to regress infarction-induced cardiac hypertrophy and HF.
Topics: Humans; Mice; Animals; Heart Failure; Myocardial Infarction; Myocytes, Cardiac; Cardiomegaly
PubMed: 37857609
DOI: 10.1038/s41392-023-01660-9 -
Cells Jul 2023Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to cardiac arrhythmia and sudden death. While... (Review)
Review
Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to cardiac arrhythmia and sudden death. While physiological cardiac hypertrophy is adaptive, hypertrophy resulting from conditions comprising hypertension, aortic stenosis, or genetic mutations, such as hypertrophic cardiomyopathy, is maladaptive. Here, we highlight the essential role and reciprocal interactions involving both cardiomyocytes and non-myocardial cells in response to pathological conditions. Prolonged cardiovascular stress causes cardiomyocytes and non-myocardial cells to enter an activated state releasing numerous pro-hypertrophic, pro-fibrotic, and pro-inflammatory mediators such as vasoactive hormones, growth factors, and cytokines, i.e., commencing signaling events that collectively cause cardiac hypertrophy. Fibrotic remodeling is mediated by cardiac fibroblasts as the central players, but also endothelial cells and resident and infiltrating immune cells enhance these processes. Many of these hypertrophic mediators are now being integrated into computational models that provide system-level insights and will help to translate our knowledge into new pharmacological targets. This perspective article summarizes the last decades' advances in cardiac hypertrophy research and discusses the herein-involved complex myocardial microenvironment and signaling components.
Topics: Humans; Endothelial Cells; Cardiomegaly; Myocardium; Myocytes, Cardiac; Heart Failure; Fibrosis
PubMed: 37443814
DOI: 10.3390/cells12131780 -
Medicine and Science in Sports and... Dec 2023This study aimed to compare the effects of free-weight and machine-based resistance training on strength, hypertrophy, and joint discomfort.
PURPOSE
This study aimed to compare the effects of free-weight and machine-based resistance training on strength, hypertrophy, and joint discomfort.
METHODS
Thirty-eight resistance-trained men participated in an 8-wk resistance program allocated into free-weight ( n = 19) or machine-based ( n = 19) groups. Training variables were identical for both modalities, so they only differed in the use of barbells or machines to execute the full squat, bench press, prone bench pull, and shoulder press exercises. The velocity-based method was implemented to accurately adjust the intensity throughout the program. Strength changes were evaluated using eight velocity-monitored loading tests (four exercises × two modalities) and included the relative one-repetition maximum (1RM Rel ), as well as the mean propulsive velocity against low (MPV Low ) and high (MPV High ) loads. Ultrasound-derived cross-sectional area of quadriceps (proximal and distal regions), pectoralis major, and rectus abdominis was measured to examine hypertrophy. Complementarily, Western Ontario and McMaster Universities and Disabilities of the Arm, Shoulder and Hand questionnaires were administrated to assess changes in lower- and upper-limb joint discomfort. Outcomes were compared using ANCOVA and percentage of change (∆) statistics.
RESULTS
Each group significantly ( P < 0.001) increased 1RM Rel , MPV Low , and MPV High for both modalities tested, but especially in the one they trained. When considering together the eight exercises tested, strength changes for both modalities were similar (∆ differences ≤1.8%, P ≥ 0.216). Likewise, the cross-sectional area of all the muscles evaluated was significantly increased by both modalities, with no significant differences between them (∆ difference ≤2.0%, P ≥ 0.208). No between-group differences ( P ≥ 0.144) were found for changes in stiffness, pain, and functional disability levels, which were reduced by both modalities.
CONCLUSIONS
Free-weight and machine-based modalities are similarly effective to promote strength and hypertrophy without increasing joint discomfort.
Topics: Male; Humans; Muscle Strength; Quadriceps Muscle; Posture; Exercise; Hypertrophy
PubMed: 37535335
DOI: 10.1249/MSS.0000000000003271 -
Journal of Sport and Health Science Jan 2024The aim of this umbrella review was to determine the impact of resistance training (RT) and individual RT prescription variables on muscle mass, strength, and physical... (Review)
Review
PURPOSE
The aim of this umbrella review was to determine the impact of resistance training (RT) and individual RT prescription variables on muscle mass, strength, and physical function in healthy adults.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass (or its proxies), strength, and/or physical function in healthy adults aged >18 years.
RESULTS
We identified 44 systematic reviews that met our inclusion criteria. The methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews; standardized effectiveness statements were generated. We found that RT was consistently a potent stimulus for increasing skeletal muscle mass (4/4 reviews provide some or sufficient evidence), strength (4/6 reviews provided some or sufficient evidence), and physical function (1/1 review provided some evidence). RT load (6/8 reviews provided some or sufficient evidence), weekly frequency (2/4 reviews provided some or sufficient evidence), volume (3/7 reviews provided some or sufficient evidence), and exercise order (1/1 review provided some evidence) impacted RT-induced increases in muscular strength. We discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass, while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle mass. There was insufficient evidence to conclude that time of day, periodization, inter-set rest, set configuration, set end point, contraction velocity/time under tension, or exercise order (only pertaining to hypertrophy) influenced skeletal muscle adaptations. A paucity of data limited insights into the impact of RT prescription variables on physical function.
CONCLUSION
Overall, RT increased muscle mass, strength, and physical function compared to no exercise. RT intensity (load) and weekly frequency impacted RT-induced increases in muscular strength but not muscle hypertrophy. RT volume (number of sets) influenced muscular strength and hypertrophy.
Topics: Adult; Humans; Resistance Training; Exercise Therapy; Exercise; Hypertrophy; Muscle, Skeletal
PubMed: 37385345
DOI: 10.1016/j.jshs.2023.06.005