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Acta Biochimica Et Biophysica Sinica Jun 2016Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of... (Review)
Review
Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy.
Topics: Animals; Autophagy; Cardiomegaly; Disease Models, Animal; Models, Cardiovascular; Myocytes, Cardiac; Signal Transduction
PubMed: 27084518
DOI: 10.1093/abbs/gmw025 -
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 -
International Journal of Molecular... Nov 2022Oxidative stress and inflammation are associated with skeletal muscle function decline with ageing or disease or inadequate exercise and/or poor diet. Paradoxically,... (Review)
Review
Oxidative stress and inflammation are associated with skeletal muscle function decline with ageing or disease or inadequate exercise and/or poor diet. Paradoxically, reactive oxygen species and inflammatory cytokines are key for mounting the muscular and systemic adaptive responses to endurance and resistance exercise. Both ageing and lifestyle-related metabolic dysfunction are strongly linked to exercise redox and hypertrophic insensitivity. The adaptive inability and consequent exercise intolerance may discourage people from physical training resulting in a vicious cycle of under-exercising, energy surplus, chronic mitochondrial stress, accelerated functional decline and increased susceptibility to serious diseases. Skeletal muscles are malleable and dynamic organs, rewiring their metabolism depending on the metabolic or mechanical stress resulting in a specific phenotype. Endogenous RNA silencing molecules, microRNAs, are regulators of these metabolic/phenotypic shifts in skeletal muscles. Skeletal muscle microRNA profiles at baseline and in response to exercise have been observed to differ between adult and older people, as well as trained vs. sedentary individuals. Likewise, the circulating microRNA blueprint varies based on age and training status. Therefore, microRNAs emerge as key regulators of metabolic health/capacity and hormetic adaptability. In this narrative review, we summarise the literature exploring the links between microRNAs and skeletal muscle, as well as systemic adaptation to exercise. We expand a mathematical model of microRNA burst during adaptation to exercise through supporting data from the literature. We describe a potential link between the microRNA-dependent regulation of redox-signalling sensitivity and the ability to mount a hypertrophic response to exercise or nutritional cues. We propose a hypothetical model of endurance exercise-induced microRNA "memory cloud" responsible for establishing a landscape conducive to aerobic as well as anabolic adaptation. We suggest that regular aerobic exercise, complimented by a healthy diet, in addition to promoting mitochondrial health and hypertrophic/insulin sensitivity, may also suppress the glycolytic phenotype and mTOR signalling through miRNAs which in turn promote systemic metabolic health.
Topics: Humans; MicroRNAs; Muscle, Skeletal; Exercise; Circulating MicroRNA; Signal Transduction; Hypertrophy
PubMed: 36499053
DOI: 10.3390/ijms232314716 -
The Journal of Physiology Jun 2023Considerable inter-individual heterogeneity exists in the muscular adaptations to resistance training. It has been proposed that fast-twitch fibres are more sensitive to...
Considerable inter-individual heterogeneity exists in the muscular adaptations to resistance training. It has been proposed that fast-twitch fibres are more sensitive to hypertrophic stimuli and thus that variation in muscle fibre type composition is a contributing factor to the magnitude of training response. This study investigated if the inter-individual variability in resistance training adaptations is determined by muscle typology and if the most appropriate weekly training frequency depends on muscle typology. In strength-training novices, 11 slow (ST) and 10 fast typology (FT) individuals were selected by measuring muscle carnosine with proton magnetic resonance spectroscopy. Participants trained both upper arm and leg muscles to failure at 60% of one-repetition maximum (1RM) for 10 weeks, whereby one arm and leg trained 3×/week and the contralateral arm and leg 2×/week. Muscle volume (MRI-based 3D segmentation), maximal dynamic strength (1RM) and fibre type-specific cross-sectional area (vastus lateralis biopsies) were evaluated. The training response for total muscle volume (+3 to +14%), fibre size (-19 to +22%) and strength (+17 to +47%) showed considerable inter-individual variability, but these could not be attributed to differences in muscle typology. However, ST individuals performed a significantly higher training volume to gain these similar adaptations than FT individuals. The limb that trained 3×/week had generally more pronounced hypertrophy than the limb that trained 2×/week, and there was no interaction with muscle typology. In conclusion, muscle typology cannot explain the high variability in resistance training adaptations when training is performed to failure at 60% of 1RM. KEY POINTS: This study investigated the influence of muscle typology (muscle fibre type composition) on the variability in resistance training adaptations and on its role in the individualization of resistance training frequency. We demonstrate that an individual's muscle typology cannot explain the inter-individual variability in resistance training-induced increases in muscle volume, maximal dynamic strength and fibre cross-sectional area when repetitions are performed to failure. Importantly, slow typology individuals performed a significantly higher training volume to obtain similar adaptations compared to fast typology individuals. Muscle typology does not determine the most appropriate resistance training frequency. However, regardless of muscle typology, an additional weekly training (3×/week vs. 2×/week) increases muscle hypertrophy but not maximal dynamic strength. These findings expand on our understanding of the underlying mechanisms for the large inter-individual variability in resistance training adaptations.
Topics: Humans; Resistance Training; Muscle, Skeletal; Muscle Fibers, Skeletal; Quadriceps Muscle; Adaptation, Physiological; Hypertrophy; Muscle Strength
PubMed: 37038845
DOI: 10.1113/JP284442 -
Medicine and Science in Sports and... Jul 2018The myonuclear domain theory postulates that myonuclei are added to muscle fibers when increases in fiber cross-sectional area (i.e., hypertrophy) are ≥26%. However,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The myonuclear domain theory postulates that myonuclei are added to muscle fibers when increases in fiber cross-sectional area (i.e., hypertrophy) are ≥26%. However, recent studies have reported increased myonuclear content with lower levels (e.g., 12%) of muscle fiber hypertrophy.
PURPOSE
This study aimed to determine whether a muscle fiber hypertrophy "threshold" is required to drive the addition of new myonuclei to existing muscle fibers.
METHODS
Studies of resistance training endurance training with or without nutrient (i.e., protein) supplementation and steroid administration with measures of muscle fiber hypertrophy and myonuclei number as primary or secondary outcomes were considered. Twenty-seven studies incorporating 62 treatment groups and 903 subjects fulfilled the inclusion criteria and were included in the analyses.
RESULTS
Muscle fiber hypertrophy of ≤10% induces increases in myonuclear content, although a significantly higher number of myonuclei are observed when muscle hypertrophy is ~22%. Additional analyses showed that age, sex, and muscle fiber type do not influence muscle fiber hypertrophy or myonuclei addition.
CONCLUSIONS
Although a more consistent myonuclei addition occurs when muscle fiber hypertrophy is >22%, our results challenge the concept of a muscle hypertrophy threshold as significant myonuclei addition occurs with lower muscle hypertrophy (i.e., <10%).
Topics: Cell Nucleus; Humans; Hypertrophy; Muscle Fibers, Skeletal; Muscle, Skeletal; Resistance Training; Satellite Cells, Skeletal Muscle
PubMed: 29509639
DOI: 10.1249/MSS.0000000000001593 -
Heart Rhythm Sep 2023
Topics: Humans; Heart; Myocardium; Cardiomegaly
PubMed: 37247687
DOI: 10.1016/j.hrthm.2023.05.029 -
Matrix Biology : Journal of the... Feb 2022The regulation of skeletal muscle growth following pro-hypertrophic stimuli requires a coordinated response by different cell types that leads to extracellular matrix...
The regulation of skeletal muscle growth following pro-hypertrophic stimuli requires a coordinated response by different cell types that leads to extracellular matrix (ECM) remodeling and increases in muscle cross-sectional area. Indeed, matricellular proteins serve a key role as communication vehicles that facilitate the propagation of signaling stimuli required for muscle adaptation to environmental challenges. We found that the matricellular protein cellular communication network factor 2 (CCN2), also known as connective tissue growth factor (CTGF), is induced during a time course of overload-driven skeletal muscle hypertrophy in mice. To elucidate the role of CCN2 in mediating the hypertrophic response, we utilized genetically engineered mouse models for myofiber-specific CCN2 gain- and loss-of-function and then examined their response to mechanical stimuli through muscle overload. Interestingly, myofiber-specific deletion of CCN2 blunted muscle's hypertrophic response to overload without interfering with ECM deposition. On the other hand, when in excess through transgenic CCN2 overexpression, CCN2 was efficient in promoting overload-induced aberrant ECM accumulation without affecting myofiber growth. Altogether, our genetic approaches highlighted independent ECM and myofiber stress adaptation responses, and positioned CCN2 as a central mediator of both. Mechanistically, CCN2 acts by regulating focal adhesion kinase (FAK) mediated transduction of overload-induced extracellular signals, including interleukin 6 (IL6), and their regulatory impact on global protein synthesis in skeletal muscle. Overall, our study highlights the contribution of muscle-derived extracellular matrix factor CCN2 for proper hypertrophic muscle growth.
Topics: Animals; Connective Tissue Growth Factor; Extracellular Matrix; Hypertrophy; Mice; Muscle, Skeletal; Signal Transduction
PubMed: 35045313
DOI: 10.1016/j.matbio.2022.01.003 -
Tissue Engineering. Part A May 2023Skeletal muscle is highly adaptive to mechanical stress due to its resident stem cells and the pronounced level of myotube plasticity. Herein, we study the adaptation to...
Skeletal muscle is highly adaptive to mechanical stress due to its resident stem cells and the pronounced level of myotube plasticity. Herein, we study the adaptation to mechanical stress and its underlying molecular mechanisms in a tissue-engineered skeletal muscle model. We subjected differentiated 3D skeletal muscle-like constructs to cyclic tensile stress using a custom-made bioreactor system, which resulted in immediate activation of stress-related signal transducers (Erk1/2, p38). Cell cycle re-entry, increased proliferation, and onset of myogenesis indicated subsequent myoblast activation. Furthermore, elevated focal adhesion kinase and β-catenin activity in mechanically stressed constructs suggested increased cell adhesion and migration. After 3 days of mechanical stress, gene expression of the fusogenic markers MyoMaker and MyoMixer, myotube diameter, myonuclear accretion, as well as S6 activation, were significantly increased. Our results highlight that we established a promising tool to study sustained adaptation to mechanical stress in healthy, hypertrophic, or regenerating skeletal muscle. Impact statement Sustained adaption to mechanical stress presents a key feature for skeletal muscle functionality and growth. Knowledge of these processes, however, is mostly based on or 2D cell culture models, both of which entail significant shortcomings. Herein, we generated highly hypertrophic tissue-engineered skeletal muscle-like constructs that are comparable to the results of successful models of adaption to mechanical stimuli, achieving an outcome that only few approaches have reached. Second, we aimed at studying the underlying molecular mechanisms, which is of interest since there is little knowledge of the intracellular events during hypertrophy upon mechanical stimulation.
Topics: Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Cell Differentiation; Tissue Engineering; Hypertrophy
PubMed: 36606693
DOI: 10.1089/ten.TEA.2022.0182 -
Cell Stem Cell Feb 2022Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for...
Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for efficient muscle hypertrophy relies on prior activation and proliferation of muscle stem cells (MuSCs). However, the mechanisms controlling MuSC expansion under conditions of increased load are not fully understood. Here we demonstrate that interstitial mesenchymal progenitors respond to mechanical load and stimulate MuSC proliferation in a surgical mouse model of increased muscle load. Mechanistically, transcriptional activation of Yes-associated protein 1 (Yap1)/transcriptional coactivator with PDZ-binding motif (Taz) in mesenchymal progenitors results in local production of thrombospondin-1 (Thbs1), which, in turn, drives MuSC proliferation through CD47 signaling. Under homeostatic conditions, however, CD47 signaling is insufficient to promote MuSC proliferation and instead depends on prior downregulation of the Calcitonin receptor. Our results suggest that relayed signaling between mesenchymal progenitors and MuSCs through a Yap1/Taz-Thbs1-CD47 pathway is critical to establish the supply of MuSCs during muscle hypertrophy.
Topics: Animals; CD47 Antigen; Hypertrophy; Mice; Muscle, Skeletal; Myoblasts; Stem Cells
PubMed: 34856120
DOI: 10.1016/j.stem.2021.11.003 -
Journal of Cachexia, Sarcopenia and... Jun 2024Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been...
BACKGROUND
Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism.
METHODS
Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)-treated and AGE-treated groups. Mice in the AGE-treated group were intraperitoneally administered AGEs (0.5 mg/g) once daily, whereas those in the BSA-treated group received an equal amount of BSA (0.5 mg/g) as the vehicle control. After 7 days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7 days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1 mg/mL) to examine cell adhesion and cell membrane permeability.
RESULTS
Continuous AGE administration increased the levels of fluorescent AGEs, Nε-(carboxymethyl) lysine, and methylglyoxal-derived hydroimidazolone-1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross-sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE-treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K-means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin-glycoprotein complex proteins and cell adhesion-related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability.
CONCLUSIONS
This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain.
Topics: Animals; Mice; Muscle, Skeletal; Glycation End Products, Advanced; Hypertrophy; Cell Membrane; Male; Disease Models, Animal
PubMed: 38575520
DOI: 10.1002/jcsm.13444