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Leucine has gained recognition as an athletic dietary supplement in recent years due to its various benefits; however, the underlying molecular mechanisms remain unclear. In this study, 20 basketball players were recruited and randomly assigned to two groups. Baseline exercise performance—assessed through a 282-foot sprint, free throws, three-point field goals, and self-rated practice assessments—was measured prior to leucine supplementation. Participants were then given a functional drink containing either leucine (50 mg/kg body weight) or a placebo for 28 days. After supplementation, the same exercise performance metrics were reassessed. Following leucine supplementation, biceps brachii muscle tissue from both groups was collected for transcriptome sequencing and qPCR verification. Our results suggested that leucine supplementation significantly improved 282-foot sprint performance, reducing times from 17.4 ± 0.9 to 16.2 ± 0.9 seconds in the leucine group, compared to minimal changes in the control group (from 17.3 ± 0.9 to 17.1 ± 0.8 seconds; P = 0.034). For other exercise performance metrics, no significant differences were observed (P > 0.05); however, trends toward improvement were noted. Transcriptomic analysis revealed 3,658 differentially expressed genes (DEGs) between the two groups. These DEGs were enriched in pathways related to immune response (P < 0.0001), positive regulation of cytokine production (P < 0.0001), and neutrophil extracellular trap formation (P < 0.0001), among others. Weighted Gene Co-expression Network Analysis (WGCNA) identified a module (turquoise) strongly associated with muscle growth, with DEGs in this module enriched in cytoskeletal pathways in muscle cells. Gene expression changes ( α-tubulin , β-tubulin , CK18 , CK8 , vimentin , cofilin , gelsolin , profilin , MAP1 , MAP2 , MAP4 , E-cadherin , and N-cadherin ) were verified by qPCR. In summary, leucine supplementation improved exercise performance, particularly by significantly reducing sprint times and showing trends of improvement in other performance metrics, including three-point field goals, free throws, and self-rated well-being. Identified DEGs enriched in pathways related to immune response, cytokine production, and cell adhesion. WGCNA highlighted a key module associated with muscle growth, enriched in cytoskeletal pathways. qPCR validation confirmed the upregulation of cytoskeleton-related genes, supporting the transcriptomic findings. These results suggest that leucine enhances muscle adaptation by regulating cytoskeletal dynamics, providing molecular insights into its role in improving athletic performance.

Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84–amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein. Myomixer together with Myomaker can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion. We conclude that the Myomixer-Myomaker pair controls the critical step in myofiber formation during muscle development.

Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration.

Extensive analyses of mice carrying null mutations in paired box 7 (Pax7) have confirmed the progressive loss of the satellite cell lineage in skeletal muscle, resulting in severe muscle atrophy and death. A recent study using floxed alleles and tamoxifen-induced inactivation concluded that after 3 wk of age, Pax7 was entirely dispensable for satellite cell function. Here, we demonstrate that Pax7 is an absolute requirement for satellite cell function in adult skeletal muscle. Following Pax7 deletion, satellite cells and myoblasts exhibit cell-cycle arrest and dysregulation of myogenic regulatory factors. Maintenance of Pax7 deletion through continuous tamoxifen administration prevented regrowth of Pax7-expressing satellite cells and a profound muscle regeneration deficit that resembles the phenotype of skeletal muscle following genetically engineered ablation of satellite cells. Therefore, we conclude that Pax7 is essential for regulating the expansion and differentiation of satellite cells during both neonatal and adult myogenesis.

Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue injuries. However, the healing mechanism is unclear. Here we assessed the effects of HBO on contused calf muscles in a rat skeletal muscle injury model. An experimental HBO chamber was developed and rats were treated with 100% oxygen, 2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb volume and muscle wet weight in contused muscles, and promoted muscle isometric strength 7 days after injury. HBO suppressed the elevation of circulating macrophages in the acute phase and then accelerated macrophage invasion into the contused muscle. This environment also increased the number of proliferating and differentiating satellite cells and the amount of regenerated muscle fibers. In the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused muscles. Our results demonstrate that HBO has a dual role in decreasing inflammation and accelerating myogenesis in muscle contusion injuries.

Schoenfeld, BJ. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res 24(10)2857-2875, 2010-The quest to increase lean body mass is widely pursued by those who lift weights. Research is lacking, however, as to the best approach for maximizing exercise-induced muscle growth. Bodybuilders generally train with moderate loads and fairly short rest intervals that induce high amounts of metabolic stress. Powerlifters, on the other hand, routinely train with high-intensity loads and lengthy rest periods between sets. Although both groups are known to display impressive muscularity, it is not clear which method is superior for hypertrophic gains. It has been shown that many factors mediate the hypertrophic process and that mechanical tension, muscle damage, and metabolic stress all can play a role in exercise-induced muscle growth. Therefore, the purpose of this paper is twofold(a) to extensively review the literature as to the mechanisms of muscle hypertrophy and their application to exercise training and (b) to draw conclusions from the research as to the optimal protocol for maximizing muscle growth.

Cell-cell interactions mediated by Notch are critical for the maintenance of skeletal muscle stem cells. However, dynamics, cellular source and identity of functional Notch ligands during expansion of the stem cell pool in muscle growth and regeneration remain poorly characterized. Here we demonstrate that oscillating Delta-like 1 (Dll1) produced by myogenic cells is an indispensable Notch ligand for self-renewal of muscle stem cells in mice. Dll1 expression is controlled by the Notch target Hes1 and the muscle regulatory factor MyoD. Consistent with our mathematical model, our experimental analyses show that Hes1 acts as the oscillatory pacemaker, whereas MyoD regulates robust Dll1 expression. Interfering with Dll1 oscillations without changing its overall expression level impairs self-renewal, resulting in premature differentiation of muscle stem cells during muscle growth and regeneration. We conclude that the oscillatory Dll1 input into Notch signaling ensures the equilibrium between self-renewal and differentiation in myogenic cell communities. The cell source and dynamics of Notch ligands during the regulation of muscle stem cells is unclear. Here, the authors show that the Notch ligand Dll1 has to oscillate in order to control the balance between self-renewal and differentiation of muscle stem cells, with Hes1 acting as transcriptional pacemaker for the oscillatory network.

Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5 , a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-γ (peroxisome-proliferator-activated receptor-γ) and activating its transcriptional function. Finally, Prdm16 -deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.

Following skeletal muscle damage, a population of resident fibro/adipogenic progenitors (FAP) initiates proliferation, resulting in the generation of ectopic white fat but not myofibres. FAPs enhance the differentiation of the myogenic progenitors involved in muscle regeneration. Efficient tissue regeneration is dependent on the coordinated responses of multiple cell types. Here, we describe a new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage. Transplantation of purified FAPs results in the generation of ectopic white fat when delivered subcutaneously or intramuscularly in a model of fatty infiltration, but not in healthy muscle, suggesting that the environment controls their engraftment. These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors.

Background Muscle development is a key factor influencing the growth performance of piglets. Optimizing this developmental process is crucial for enhancing breeding efficiency and economic profitability. Tryptophan (Trp) is considered one of the key limiting amino acids for weaned piglets, plays an essential role in regulating feed intake, growth, and muscle development. However, the regulatory mechanisms by which Trp and its derivatives influence muscle development in weaned piglets remain unclear. Methods The aim of this study was to investigate the regulatory pathways and potential mechanisms of Trp and its metabolites on muscle development in weaned piglets. In this study, 10 healthy castrated male piglets, 28 days old and weaned, were selected and randomly assigned to a control group (CON, 0.14% Trp) and a high tryptophan group (HT, 0.35% Trp), with 5 in each group. After a 7-day pre-feeding period, the formal feeding began, and after 28 days, the pigs were slaughtered and the longissimus dorsi muscles was collected for transcriptome sequencing. Results The results indicated that different dietary Trp levels led to the identification of sixteen differentially expressed microRNAs (DE miRNAs) in the longissimus dorsi muscle of the weaned piglets. Target gene functional enrichment analysis showed that these DE miRNAs are involved in muscle cell proliferation, differentiation, protein deposition, and muscle development through multiple biological pathways. Furthermore, we constructed a protein-protein interaction (PPI) network for the target genes, with the enriched core gene cluster functions associated with cellular proliferation, signaling pathways, hormone release, and muscle development. Finally, qRT-PCR validated the reliability and accuracy of the RNA-seq results, revealing a correlation coefficient of 0.97 between the two methods. Conclusions This study uncovers the potential mechanisms by which miRNAs participate in the regulation of muscle development in weaned piglets mediated by Trp and its metabolites, providing a theoretical basis and practical guidance for optimizing piglet management and health improvement.