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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 -
Journal of Advanced Research Sep 2023Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles in obesity, insulin resistance, and inflammation....
INTRODUCTION
Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles in obesity, insulin resistance, and inflammation. Metrnl is found to protect against cardiac hypertrophy and doxorubicin-induced cardiotoxicity. However, its role in diabetic cardiomyopathy (DCM) is undefined.
OBJECTIVES
We aimed to elucidate the potential roles of Metrnl in DCM.
METHODS
Gain- andloss-of-function experimentswere utilized to determine the roles of Metrnl in the pathological processes of DCM.
RESULTS
We found that plasma Metrnl levels, myocardial Metrnl protein and mRNA expressions were significantly downregulated in both streptozotocin (STZ)-induced (T1D) mice and leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) of Metrnl markedly ameliorated cardiac injury and dysfunction in both T1D and T2D mice. In sharp contrast, specific deletion of Metrnl in the heart had the opposite phenotypes. In parallel, Metrnl OE ameliorated, whereas Metrnl downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis and oxidative damage in primary neonatal rat cardiomyocytes. Antibody-induced blockade of Metrnl eliminated the effects of benefits of Metrnl in vitro and in vivo. Mechanistically, Metrnl activated the autophagy pathway and inhibited the cGAS/STING signaling in a LKB1/AMPK/ULK1-dependent mechanism in cardiomyocytes. Besides, Metrnl-induced ULK1 phosphorylation facilitated the dephosphorylation and mitochondrial translocation of STING where it interacted with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase that was responsible for ubiquitination and degradation of STING, rendering cardiomyocytes sensitive to autophagy activation.
CONCLUSION
Thus, Metrnl may be an attractive therapeutic target or regimen for treating DCM.
Topics: Animals; Mice; Rats; AMP-Activated Protein Kinases; Autophagy; Autophagy-Related Protein-1 Homolog; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Myocytes, Cardiac; Nucleotidyltransferases
PubMed: 36334887
DOI: 10.1016/j.jare.2022.10.014 -
Journal of Functional Morphology and... Dec 2023Regimented resistance training (RT) has been shown to promote increases in muscle size. When engaging in RT, practitioners often emphasize the importance of appropriate... (Review)
Review
Regimented resistance training (RT) has been shown to promote increases in muscle size. When engaging in RT, practitioners often emphasize the importance of appropriate exercise technique, especially when trying to maximize training adaptations (e.g., hypertrophy). This narrative review aims to synthesize existing evidence on what constitutes proper RT exercise technique for maximizing muscle hypertrophy, focusing on variables such as exercise-specific kinematics, contraction type, repetition tempo, and range of motion (ROM). We recommend that when trying to maximize hypertrophy, one should employ a ROM that emphasizes training at long muscle lengths while also employing a repetition tempo between 2 and 8 s. More research is needed to determine whether manipulating the duration of either the eccentric or concentric phase further enhances hypertrophy. Guidelines for body positioning and movement patterns are generally based on implied theory from applied anatomy and biomechanics. However, existing research on the impact of manipulating these aspects of exercise technique and their effect on hypertrophy is limited; it is therefore suggested that universal exercise-specific kinematic guidelines are followed and adopted in accordance with the above recommendations. Future research should investigate the impact of stricter versus more lenient exercise technique variations on hypertrophy.
PubMed: 38249086
DOI: 10.3390/jfmk9010009 -
Sports Medicine (Auckland, N.Z.) Nov 2023Increasing muscle strength and cross-sectional area is of crucial importance to improve or maintain physical function in musculoskeletal rehabilitation and sports... (Review)
Review
Increasing muscle strength and cross-sectional area is of crucial importance to improve or maintain physical function in musculoskeletal rehabilitation and sports performance. Decreases in muscular performance are experienced in phases of reduced physical activity or immobilization. These decrements highlight the need for alternative, easily accessible training regimens for a sedentary population to improve rehabilitation and injury prevention routines. Commonly, muscle hypertrophy and strength increases are associated with resistance training, typically performed in a training facility. Mechanical tension, which is usually induced with resistance machines and devices, is known to be an important factor that stimulates the underlying signaling pathways to enhance protein synthesis. Findings from animal studies suggest an alternative means to induce mechanical tension to enhance protein synthesis, and therefore muscle hypertrophy by inducing high-volume stretching. Thus, this narrative review discusses mechanical tension-induced physiological adaptations and their impact on muscle hypertrophy and strength gains. Furthermore, research addressing stretch-induced hypertrophy is critically analyzed. Derived from animal research, the stretching literature exploring the impact of static stretching on morphological and functional adaptations was reviewed and critically discussed. No studies have investigated the underlying physiological mechanisms in humans yet, and thus the underlying mechanisms remain speculative and must be discussed in the light of animal research. However, studies that reported functional and morphological increases in humans commonly used stretching durations of > 30 min per session of the plantar flexors, indicating the importance of high stretching volume, if the aim is to increase muscle mass and maximum strength. Therefore, the practical applicability seems limited to settings without access to resistance training (e.g., in an immobilized state at the start of rehabilitation), as resistance training seems to be more time efficient. Nevertheless, further research is needed to generate evidence in different human populations (athletes, sedentary individuals, and rehabilitation patients) and to quantify stretching intensity.
PubMed: 37556026
DOI: 10.1007/s40279-023-01898-x -
BioRxiv : the Preprint Server For... Jul 2023We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes.
PURPOSE
We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes.
METHODS
Untrained college-aged participants were randomized into HT or SQ groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed nine weeks of supervised training (15-17 sessions), before and after which we assessed muscle cross-sectional area (mCSA) via magnetic resonance imaging and strength via three-repetition maximum (3RM) testing and an isometric wall push test.
RESULTS
Glutei mCSA growth was similar across both groups. Estimates [(-) favors HT; (+) favors SQ] modestly favored the HT compared to SQ for lower [effect ± SE, -1.6 ± 2.1 cm], mid [-0.5± 1.7 cm], and upper [-0.5 ± 2.6 cm], but with appreciable variance. Gluteus medius+minimus [-1.8 ± 1.5 cm] and hamstrings [0.1 ± 0.6 cm] mCSA demonstrated little to no growth with small differences between groups. Thigh mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm] and adductors [2.5 ± 0.7 cm]. Squat 3RM increases favored SQ [14 ± 2.5 kg] and hip thrust 3RM favored HT [-26 ± 5 kg]. 3RM deadlift [0 ± 2 kg] and wall push strength [-7 ± 13 N] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes.
CONCLUSION
Nine weeks of squat versus hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar strength transfers to the deadlift and wall push.
PubMed: 37461495
DOI: 10.1101/2023.06.21.545949 -
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