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Journal of Applied Physiology... Jul 2016We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and...
We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether postexercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (23 ± 1 yr, mean ± SE) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ∼30-50% of their maximal strength (1RM) for 20-25 repetitions/set (n = 24) or a lower-repetition (LR) group (∼75-90% 1RM, 8-12 repetitions/set, n = 25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, dual-energy X-ray absorptiometry scans, and acute changes in systemic hormone concentrations were examined pretraining and posttraining. In response to RT, 1RM strength increased for all exercises in both groups (P < 0.01), with only the change in bench press being significantly different between groups (HR, 9 ± 1, vs. LR, 14 ± 1 kg, P = 0.012). Fat- and bone-free (lean) body mass and type I and type II muscle fiber cross-sectional area increased following training (P < 0.01) with no significant differences between groups. No significant correlations between the acute postexercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute postexercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals, load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains.
Topics: Adult; Exercise; Hormones; Humans; Hypertrophy; Male; Muscle Strength; Muscle, Skeletal; Resistance Training; Weight Lifting; Young Adult
PubMed: 27174923
DOI: 10.1152/japplphysiol.00154.2016 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Skeletal Muscle Jul 2022Skeletal muscle homeostasis and function are ensured by orchestrated cellular interactions among several types of cells. A noticeable aspect of skeletal muscle biology... (Review)
Review
Skeletal muscle homeostasis and function are ensured by orchestrated cellular interactions among several types of cells. A noticeable aspect of skeletal muscle biology is the drastic cell-cell communication changes that occur in multiple scenarios. The process of recovering from an injury, which is known as regeneration, has been relatively well investigated. However, the cellular interplay that occurs in response to mechanical loading, such as during resistance training, is poorly understood compared to regeneration. During muscle regeneration, muscle satellite cells (MuSCs) rebuild multinuclear myofibers through a stepwise process of proliferation, differentiation, fusion, and maturation, whereas during mechanical loading-dependent muscle hypertrophy, MuSCs do not undergo such stepwise processes (except in rare injuries) because the nuclei of MuSCs become directly incorporated into the mature myonuclei. In this review, six specific examples of such differences in MuSC dynamics between regeneration and hypertrophy processes are discussed.
Topics: Cell Differentiation; Humans; Hypertrophy; Muscle, Skeletal; Myoblasts; Regeneration
PubMed: 35794679
DOI: 10.1186/s13395-022-00300-0 -
JACC. Cardiovascular Imaging Nov 2019Pathological left ventricular hypertrophy is a common feature of many cardiac diseases. It results from both myocyte hypertrophy and interstitial expansion. Interstitial... (Review)
Review
Pathological left ventricular hypertrophy is a common feature of many cardiac diseases. It results from both myocyte hypertrophy and interstitial expansion. Interstitial expansion is most commonly secondary to the accumulation of mature cross-linked collagen fibers due to dysregulated metabolism, known as interstitial fibrosis. This occurs secondary to a variety of stimuli including ischemic, toxic, metabolic, infective, genetic, and hemodynamic factors. Less commonly, interstitial expansion may occur because of the accumulation of misfolded amyloid protein or interstitial edema. It is now well recognized that the presence and extent of interstitial disease are associated with adverse outcomes. There is therefore interest in the development of novel therapies that target the pathways that drive these disease processes. With the emergence of such therapies, it is becoming increasingly important to be able to characterize the type and extent of interstitial disease to enable the use of such targeted therapies in a personalized manner.
Topics: Biopsy; Extracellular Space; Fibrosis; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Myocardium; Tomography, Emission-Computed; Ventricular Function, Left; Ventricular Remodeling
PubMed: 31542527
DOI: 10.1016/j.jcmg.2019.05.033 -
Physiological Reports Oct 2022Skeletal muscle is a plastic tissue that regenerates ad integrum after injury and adapts to raise mechanical loading/contractile activity by increasing its mass and/or... (Review)
Review
Skeletal muscle is a plastic tissue that regenerates ad integrum after injury and adapts to raise mechanical loading/contractile activity by increasing its mass and/or myofiber size, a phenomenon commonly refers to as skeletal muscle hypertrophy. Both muscle regeneration and hypertrophy rely on the interactions between muscle stem cells and their neighborhood, which include inflammatory cells, and particularly macrophages. This review first summarizes the role of macrophages in muscle regeneration in various animal models of injury and in response to exercise-induced muscle damage in humans. Then, the potential contribution of macrophages to skeletal muscle hypertrophy is discussed on the basis of both animal and human experiments. We also present a brief comparative analysis of the role of macrophages during muscle regeneration versus hypertrophy. Finally, we summarize the current knowledge on the impact of different immunomodulatory strategies, such as heat therapy, cooling, massage, nonsteroidal anti-inflammatory drugs and resolvins, on skeletal muscle regeneration and their potential impact on muscle hypertrophy.
Topics: Animals; Anti-Inflammatory Agents; Humans; Hypertrophy; Macrophages; Muscle, Skeletal; Plastics; Regeneration
PubMed: 36200266
DOI: 10.14814/phy2.15480 -
European Journal of Sport Science Sep 2016Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great... (Review)
Review
Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.
Topics: Exercise; Humans; Hypertrophy; Muscle, Skeletal; Resistance Training
PubMed: 26289597
DOI: 10.1080/17461391.2015.1073362 -
Cardiovascular Journal of AfricaWe aimed to evaluate and compare papillary muscle free strain in hypertrophic cardiomyopathy (HCMP) and hypertensive (HT) patients.
OBJECTIVES
We aimed to evaluate and compare papillary muscle free strain in hypertrophic cardiomyopathy (HCMP) and hypertensive (HT) patients.
METHODS
Global longitudinal strain (GLS), and longitudinal myocardial strain of the anterolateral (ALPM) and posteromedial papillary muscles (PMPM) were obtained in 46 HCMP and 50 HT patients.
RESULTS
Interventricular septum (IVS)/posterior wall (PW) thickness ratio, left ventricular mass index (LVMI), left atrial anteroposterior diameter (LAAP) and mitral E/E' were found to be increased in patients with HCMP compared to HT patients. Left ventricular cavity dimensions were smaller in HCMP patients. GLS of HCMP and HT patients were - 14.52 ± 3.01 and -16.85 ± 1.36%, respectively ( < 0.001). Likewise, ALPM and PMPM free strain values were significantly reduced in HCMP patients over HT patients [-14.00% (-22 to -11%) and -15.5% (-24.02 to -10.16%) vs -23.00% (-24.99 to -19.01%) and -22.30% (-26.48 to -15.95%) ( = 0.016 and = 0.010)], respectively. ALPM free strain showed a statistically significant correlation with GLS, maximal wall thickness, IVS thickness and LVMI. PMPM free strain showed a significant correlation with GLS, IVS thickness and LAAP. The GLS value of - 13.05 had a sensitivity of 61.9% and a specificity of 97.4% for predicting HCMP. ALPM and PMPM free strain values of -15.31 and -17.17% had 63 and 76.9% sensitivity and 85.7 and 76.9% specificity for prediction of HCMP.
CONCLUSIONS
Besides other echocardiographic variables, which were investigated in earlier studies, papillary muscle free strain also could be used in HCMP to distinguish HCMP- from HT-associated hypertrophy.
Topics: Humans; Hypertrophy, Left Ventricular; Papillary Muscles; Myocardial Contraction; Cardiomyopathy, Hypertrophic; Hypertension; Ventricular Function, Left
PubMed: 36947167
DOI: 10.5830/CVJA-2022-070 -
American Journal of Physiology.... Jan 2022Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that macrophages... (Review)
Review
Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that macrophages could also present two major subsets during tissue healing: proliferative macrophages (M1-like), which are responsible for increasing myogenic cell proliferation, and restorative macrophages (M2-like), which are involved in the end of the mature muscle myogenesis. The participation and characterization of these macrophage subsets are critical during myogenesis to understand the inflammatory role of macrophages during muscle recovery and to create supportive strategies that can improve mass muscle maintenance. Indeed, most of our knowledge about macrophage subsets comes from skeletal muscle damage protocols, and we still do not know how these subsets can contribute to skeletal muscle adaptation. Thus, this narrative review aims to collect and discuss studies demonstrating the involvement of different macrophage subsets during the skeletal muscle damage/regeneration process, showcasing an essential role of these macrophage subsets during muscle adaptation induced by acute and chronic exercise programs.
Topics: Animals; Cell Proliferation; Exercise; Humans; Hypertrophy; Inflammation; Inflammation Mediators; Macrophages; Muscle, Skeletal; Phenotype; Regeneration; Signal Transduction; Skeletal Muscle Enlargement
PubMed: 34786967
DOI: 10.1152/ajpregu.00038.2021 -
Current Opinion in Clinical Nutrition... May 2011To highlight recent breakthroughs and controversies in the use of myoblast models to uncover cellular and molecular mechanisms regulating skeletal muscle hypertrophy and... (Review)
Review
PURPOSE OF REVIEW
To highlight recent breakthroughs and controversies in the use of myoblast models to uncover cellular and molecular mechanisms regulating skeletal muscle hypertrophy and atrophy.
RECENT FINDINGS
Myoblast cultures provide key mechanistic models of the signalling and molecular pathways potentially employed by skeletal muscle in-vivo to regulate hypertrophy and atrophy. Recently the controversy as to whether insulin-like growth factor (IGF)-I is important in hypertrophy following mechanical stimuli vs. alternative pathways has been hotly debated and is discussed. The role of myostatin in myoblast models of atrophy and interactions between protein synthetic pathways including Akt/mTOR and the 'atrogenes' are explored.
SUMMARY
Targeted in-vivo experimentation directed by skeletal muscle cell culture and bioengineering (three-dimensional skeletal muscle cell culture models) will provide key biomimetic and mechanistic data regarding hypertrophy and atrophy and thus enable the development of important strategies for tackling muscle wasting associated with ageing and disease processes.
Topics: Humans; Hypertrophy; Insulin-Like Growth Factor I; Models, Biological; Muscle, Skeletal; Muscular Atrophy; Myoblasts, Skeletal; Myostatin; Protein Biosynthesis; Signal Transduction; Stress, Mechanical
PubMed: 21460719
DOI: 10.1097/MCO.0b013e3283457ade -
Scientific Reports Mar 2023A systematic review and meta-analysis was conducted to determine the effects of resistance training under hypoxic conditions (RTH) on muscle hypertrophy and strength... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis was conducted to determine the effects of resistance training under hypoxic conditions (RTH) on muscle hypertrophy and strength development. Searches of PubMed-Medline, Web of Science, Sport Discus and the Cochrane Library were conducted comparing the effect of RTH versus normoxia (RTN) on muscle hypertrophy (cross sectional area (CSA), lean mass and muscle thickness) and strength development [1-repetition maximum (1RM)]. An overall meta-analysis and subanalyses of training load (low, moderate or high), inter-set rest interval (short, moderate or long) and severity of hypoxia (moderate or high) were conducted to explore the effects on RTH outcomes. Seventeen studies met inclusion criteria. The overall analyses showed similar improvements in CSA (SMD [CIs] = 0.17 [- 0.07; 0.42]) and 1RM (SMD = 0.13 [0.0; 0.27]) between RTH and RTN. Subanalyses indicated a medium effect on CSA for longer inter-set rest intervals and a small effect for moderate hypoxia and moderate loads favoring RTH. Moreover, a moderate effect for longer inter-set rest intervals and a trivial effect for severe hypoxia and moderate loads favoring RTH was found on 1RM. Evidence suggests that RTH employed with moderate loads (60-80% 1RM) and longer inter-set rest intervals (≥ 120 s) enhances muscle hypertrophy and strength compared to normoxia. The use of moderate hypoxia (14.3-16% FiO) seems to be somewhat beneficial to hypertrophy but not strength. Further research is required with greater standardization of protocols to draw stronger conclusions on the topic.
Topics: Humans; Animals; Resistance Training; Gastropoda; Hypertrophy; Hypoxia; Muscles
PubMed: 36871095
DOI: 10.1038/s41598-023-30808-4