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Physiological Reports Aug 2022Lactate is a metabolic product of glycolysis and has recently been shown to act as a signaling molecule that induces adaptations in oxidative metabolism. In this study,...
Lactate is a metabolic product of glycolysis and has recently been shown to act as a signaling molecule that induces adaptations in oxidative metabolism. In this study, we investigated whether lactate administration enhanced muscle hypertrophy and protein synthesis responses during resistance exercise in animal models. We used male ICR mice (7-8 weeks old) were used for chronic (mechanical overload induced by synergist ablation: [OL]) and acute (high-intensity muscle contraction by electrical stimulation: [ES]) resistance exercise models. The animals were intraperitoneally administrated a single dose of sodium lactate (1 g/kg of body weight) in the ES study, and once a day for 14 consecutive days in the OL study. Two weeks of mechanical overload increased plantaris muscle wet weight (main effect of OL: p < 0.05) and fiber cross-sectional area (main effect of OL: p < 0.05), but those were not affected by lactate administration. Following the acute resistance exercise by ES, protein synthesis and phosphorylation of p70 S6 kinase and ribosomal protein S6, which are downstream molecules in the anabolic signaling cascade, were increased (main effect of ES: p < 0.05), but lactate administration had no effect. This study demonstrated that exogenous lactate administration has little effect on the muscle hypertrophic response during resistance exercise using acute ES and chronic OL models. Our results do not support the hypothesis that elevated blood lactate concentration induces protein synthesis responses in skeletal muscle.
Topics: Animals; Hypertrophy; Lactic Acid; Male; Mice; Mice, Inbred ICR; Muscle, Skeletal; Phosphorylation; TOR Serine-Threonine Kinases
PubMed: 35993446
DOI: 10.14814/phy2.15436 -
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 -
Proceedings of the American Thoracic... Jan 2008Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e.,... (Review)
Review
Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.
Topics: Actins; Airway Obstruction; Airway Resistance; Animals; Asthma; Bronchial Spasm; Cell Movement; Contractile Proteins; Humans; Hyperplasia; Hypertrophy; Muscle, Smooth
PubMed: 18094090
DOI: 10.1513/pats.200705-063VS -
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 -
Critical Reviews in Biochemistry and... 2014The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network... (Review)
Review
The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.
Topics: Animals; Cachexia; Humans; Hypertrophy; Muscle, Skeletal; Muscular Atrophy; Signal Transduction
PubMed: 24237131
DOI: 10.3109/10409238.2013.857291 -
Journal of Applied Physiology... May 2020It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men; however, it remains to be determined whether... (Randomized Controlled Trial)
Randomized Controlled Trial
It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men; however, it remains to be determined whether similar morphological adaptations can be achieved in women. The aim of the present study was therefore to investigate whether exogenously administered testosterone alters muscle fiber morphology in skeletal muscle of young healthy, physically active women. Thirty-five young (20-35 yr), recreationally trained women were randomly assigned to either 10-wk testosterone administration (10 mg daily) or placebo. Before and after the intervention, hormone concentrations and body composition were assessed, and muscle biopsies were obtained from the vastus lateralis. Fiber type composition, fiber size, satellite cell and myonuclei content, as well as muscle capillarization were assessed in a fiber type-specific manner by immunohistochemistry. After the intervention, testosterone administration elevated serum testosterone concentration (5.1-fold increase, = 0.001) and induced significant accretion of total lean mass (+1.9%, = 0.002) and leg lean mass (+2.4%, = 0.001). On the muscle fiber level, testosterone increased mixed-fiber cross-sectional area (+8.2%, = 0.001), an effect primarily driven by increases in type II fiber size (9.2%, = 0.006). Whereas myonuclei content remained unchanged, a numerical increase (+30.8%) was found for satellite cells associated with type II fibers in the Testosterone group. In parallel with fiber hypertrophy, testosterone significantly increased capillary contacts (+7.5%, = 0.015) and capillary-to-fiber ratio (+9.2%, = 0.001) in type II muscle fibers. The present study provides novel insight into fiber type-specific adaptations present already after 10 wk of only moderately elevated testosterone levels in women. We have recently demonstrated performance-enhancing effects of moderately elevated testosterone concentrations in young women. Here we present novel evidence that testosterone alters muscle morphology in these women, resulting in type II fiber hypertrophy and improved capillarization. Our findings suggest that low doses of testosterone potently impact skeletal muscle after only 10 wk. These data provide unique insights into muscle adaptation and support the performance-enhancing role of testosterone in women on the muscle fiber level.
Topics: Female; Humans; Hypertrophy; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Resistance Training; Satellite Cells, Skeletal Muscle; Testosterone
PubMed: 32191598
DOI: 10.1152/japplphysiol.00893.2019 -
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 -
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 -
Scientific Reports Aug 2021This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of...
This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of such anabolic response to protein consumption is seen by the LPD this may negatively affect the skeletal muscle mass. Muscle protein synthesis (MPS) was measured by puromycin labeling in Apolipoprotein E knockout (Apoe KO), characterized by an unhealthy LPD, and wild type mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanisms were studied and gut microbiome diversity explored. Surprisingly, whey-protein feeding did not affect MPS. p-mTOR and p-4E-BP1 was increased 2 h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to wild type. At 20 weeks of age, Apoe KO had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to wild type. These responses were not associated with gut microbiota compositional differences. Regardless of LPD status, MPS was similar in Apoe KO and wild type. Surprisingly, whey-protein did not stimulate MPS. However, Apoe KO had lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.
Topics: Animals; Apolipoproteins E; Gastrointestinal Microbiome; Hypertrophy; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Whey Proteins
PubMed: 34385572
DOI: 10.1038/s41598-021-96000-8