Human Muscle Hypertrophy Research Articles

Genome-wide association study for growth-related traits in golden pompano (Trachinotus ovatus)

Growth-related traits are complex and economically important traits in the aquaculture industry. Improvement of growth traits is generally considered as the main objective in breeding programs of farmed fish. The molecular basis underlying Golden pompano (Trachinotus ovatus) growth traits remains largely unknown. T. ovatus is a commercial marine fish species with a considerable market value. It is necessary to select new varieties of T. ovatus with fast growth traits, which could contribute to increased production and lower costs. In this study, the whole genome resequencing (WGS) was applied for genotyping 716 T. ovatus individuals and 4,886,850 high-quality single nucleotide polymorphism (SNP) located on 24 chromosomes were developed. A genome-wide association study (GWAS) was performed to detect SNPs and genes that are potentially related with growth traits, including body weight (BW) and body length (BL). Results indicated that 107 SNPs were significantly associated with growth traits, of which 18 SNPs were commonly shared with BW and BL traits. Furthermore, 108 genes were annotated by the identified SNPs. GO enrichment analysis suggested that the terms related with muscle growth, anabolism, and bone development were significantly enriched. Most candidate genes were known to be involved in muscle growth and bone development, some of which were reported to be associated with muscle hypertrophy in humans. This study provides useful information to understand the genetic architecture of growth-related traits and provides effective molecular markers for future genome-wide selection breeding of T. ovatus.

Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.

BackgroundThe relative role of skeletal muscle mechano‐transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men.MethodsNon‐hypogonadal men (n = 16; 18–30 years) were randomized in a double‐blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole‐body RET. Participants underwent dual‐energy X‐ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses.ResultsZoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF‐1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF‐1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET‐induced phosphorylation of growth signalling proteins (e.g. AKTser473: Z: 2.74 ± 0.6, P = 0.2 vs. P: 5.5 ± 1.1 fold change, P < 0.001, ES = 0.54 and mTORC1ser2448: Z: 1.9 ± 0.8, P > 0.99 vs. P: 3.6 ± 1 fold change, P = 0.002, ES = 0.53). Both MPS (Z: 1.45 ± 0.11 to 1.50 ± 0.06%·day−1, P = 0.99 vs. P: 1.5 ± 0.12 to 2.0 ± 0.15%·day−1, P = 0.01, ES = 0.97) and (extrapolated) muscle protein breakdown (Z: 93.16 ± 7.8 vs. P: 129.1 ± 13.8 g·day−1, P = 0.04, ES = 0.92) were reduced with hypogonadism result in lower net protein turnover (3.9 ± 1.1 vs. 1.2 ± 1.1 g·day−1, P = 0.04, ES = 0.95).ConclusionsWe conclude that endogenous T sufficiency has a central role in the up‐regulation of molecular transducers of RET‐induced muscle hypertrophy in humans that cannot be overcome by muscle mechano‐transduction alone.

Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy

ObjectiveThe Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofibre size and function and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo before exploring the importance of VDR expression upon muscle hypertrophy in humans. MethodsWistar rats underwent in vivo electrotransfer (IVE) to overexpress the VDR in the Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20 wks of resistance exercise training, with body composition and transcriptomic analysis. ResultsMuscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area, i.e., hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling, reflecting translational efficiency (e.g., mammalian target of rapamycin (mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodelling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were upregulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training. ConclusionVDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and upregulation of ECM remodelling-related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogues.

Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans.

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans.

Does stretch training induce muscle hypertrophy in humans? A review of the literature.

Stretch training is widely used in a variety of fitness-related capacities such as increasing joint range of motion, preventing contractures and alleviating injuries. Moreover, some researches indicate that stretch training may induce muscle hypertrophy; however, studies on the topic have been primarily relegated to animal and in vitro models. The purpose of this brief review was to evaluate whether stretch training is a viable strategy to induce muscle hypertrophy in humans. An extensive literature search was performed using PubMed/MEDLINE, SciELO and Scopus databases, using terms related to stretching and muscle hypertrophy. Only human trials that evaluated changes in measures of muscle size or architecture following training protocols that it was performed stretching exercises were selected for inclusion. Of the 10 studies identified, 3 observed some significantly positive effects of stretch training on muscle structure. Intriguingly, in these studies, the stretching was carried out with an apparatus that aided in its performance, or with an external overload. In all studies, the subjects performed stretching at their own self-determined range of motion, and no effect was observed. Of the 5 available studies that integrated stretching into a resistance training programme, 2 applied the stretching in the interset rest period and were the ones that showed enhanced muscle growth. In conclusion, passive, low-intensity stretch does not appear to confer beneficial changes in muscle size and architecture; alternatively, albeit limited evidence suggests that when stretching is done with a certain degree of tensile strain (particularly when loaded, or added between active muscle contractions) may elicit muscle hypertrophy.

Isolated branched-chain amino acid intake and muscle protein synthesis in humans: a biochemical review.

ABSTRACTAlongside a proper diet, ergogenic aids with potential direct and/or indirect physical performance enhancing effects are sought after for improved adaptation to physical training. Nutritional ergogenics include diet composition changes and/or dietary supplementation. Branched-chain amino acids valine, leucine and isoleucine are widely popular among products with ergogenic claims. Their major marketing appeal derives from allegations that branched-chain amino acids intake combined with resistance physical exercise stimulates muscle protein synthesis. Evidence supporting the efficacy of branched-chain amino acids alone for muscle hypertrophy in humans is somewhat equivocal. This brief review describes physiological and biochemical mechanisms underpinning the effects of complete protein source and branched-chain amino acid intake on skeletal muscle growth in the postabsorptive and post-exercise state. Evidence in favor of or against potential anabolic effects of isolated branched-chain amino acid intake on muscle protein synthesis in humans is also examined.

Low intensity resistance exercise training with blood flow restriction: insight into cardiovascular function, and skeletal muscle hypertrophy in humans.

Attenuated functional exercise capacity in elderly and diseased populations is a common problem, and stems primarily from physical inactivity. Decreased function and exercise capacity can be restored by maintaining muscular strength and mass, which are key factors in an independent and healthy life. Resistance exercise has been used to prevent muscle loss and improve muscular strength and mass. However, the intensities necessary for traditional resistance training to increase muscular strength and mass may be contraindicated for some at risk populations, such as diseased populations and the elderly. Therefore, an alternative exercise modality is required. Recently, blood flow restriction (BFR) with low intensity resistance exercise (LIRE) has been used for such special populations to improve their function and exercise capacity. Although BFR+LIRE has been intensively studied for a decade, a comprehensive review detailing the effects of BFR+LIRE on both skeletal muscle and vascular function is not available. Therefore, the purpose of this review is to discuss previous studies documenting the effects of BFR+LIRE on hormonal and transcriptional factors in muscle hypertrophy and vascular function, including changes in hemodynamics, and endothelial function.

G.P.197: Strongman syndrome: Clinical, pathological and genetic characterization of dominant herculean myalgic disorders

Muscle mass and strength are variable traits in humans. Many French Canadians (FC) became international celebrities because of their exceptional strength. Though muscle hypertrophy has been associated in many mammals with myostatin mutations, to date only a single pediatric case has been reported in humans. Dominant pathological mutations in the CLCN1, SCN4A, CAV3, ATP2A1, LPIN1, LMNA and RYR1 gene have been known to lead to muscle hypertrophy in humans, in particular selective muscle hypertrophy in certain myopathies. These conditions are associated with either weakness or increased strength. We recruited a cohort of more than 115 cases belonging to more than 65 families of a heterogeneous dominant condition that we refer to as: "Strongman syndrome" (SM). In all families, the most affected case suffers from incapacitating myalgias with variable degree of muscle cramps, and they also have a personal and familial history of above average strength. On examination these patients have large well defined muscles, above average strength, non-electric prolonged muscle contractions and progressive weakness on repeated contractions. Exome sequencing of a large FC family identified a single segregating variant predicted to be damaging in the DCST2 gene shared also by two other FC families. The DCST2 gene is expressed in skeletal muscle and is predicted to code for a six transmembrane domains channel-like protein. To better characterize the herculean strength we assesses different biometric variables in a subset of cases with and without DCST2 mutations and investigated if myofiber hypertrophy is present. Results of quantifiable methods to evaluate the clinical and pathological phenotype of strongman cases will be presented, as well as functional data about DCST2. The uncovering of the function of DCST2 and other strongman genes will contribute to a better understanding of pathways important for muscle hypertrophy and strength in health and disease.

Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining

Myostatin is a potent negative regulator of skeletal muscle mass, but its role in human skeletal muscle hypertrophy and atrophy is sparsely described. Muscle biopsies were obtained from young male subjects before and after 30 and 90 days of resistance training as well as after 3, 10, 30, 60 and 90 days of subsequent detraining. Myostatin mRNA increased significantly with detraining. We observed a 28 kDa myostatin immunoreactive protein, which, however, was also present in myostatin knock out mice skeletal muscle. As a novel finding we consistently detected a 10 kDa band, which may represent a mature myostatin monomer under reducing conditions or a novel, unknown myostatin form. Further, we observed a significant increase in this 10 kDa band after 3 days of detraining preceding the rapid type II fiber atrophy, in which almost half of the acquired fiber area was lost after only 10 days of detraining. Accordingly, an increase in the level of the 10 kDa protein is associated with rapid type II fiber atrophy, suggesting myostatin-mediated specific type II fiber atrophy, which in combination with our mRNA data support a role for myostatin in the negative regulation of adult human skeletal muscle mass.

Point:Counterpoint: Satellite cell addition is/is not obligatory for skeletal muscle hypertrophy

Myofiber size is dynamically regulated, increasing and decreasing depending on muscle use. Hypertrophy is defined by increases in myofiber cross-sectional area and mass as well as myofibrillar protein content. Myofibers contain many hundreds of nuclei, each of which has a nuclear domain. A nuclear

The PI3K/Akt/mTOR pathway is up‐regulated during skeletal muscle hypertrophy in humans

We sought to resolve which components of the IGF1/PI3K/Akt/mTOR pathway are responsive to mechanical load and are coincident with increases in myofiber hypertrophy in vivo. A mixed-age, mixed-gender population (n = 66) of humans underwent a 16 wk lower extremity resistance training regimen. Muscle biopsies were performed at baseline and 24 h after the first and last loading bouts. Subjects were statistically clustered based on changes in mean fiber area (MFA, μm2) as non-responders (NR, n=17), modest responders (MR, +1111 μm2, n=32), and extreme responders (XR, +2475 μm2, n=17). Translation initiation signaling was assessed in a subset of 8 NR, 14 MR, and 8 XR. Data were analyzed via 3 x 3 (response cluster x time) repeated measures ANOVA. Tukey HSD tests were performed post hoc to localize main and/or interaction effects. Main time effects (P<0.05) were noted for p-Akt (+53% after 1 bout), total Akt (+31% by wk 16), total 4EBP1 (−28% by wk 16), p-eIF4E (+24% after 1 bout), total eIF4E (+15% after 1 bout), and p-eIF4G (+51% after 1 bout). p-4EBP1 tended to increase (24%, P=0.051) after 1 bout. Akt phosphorylation was 74% higher (P<0.05) and mTOR expression tended to be higher (44%, P=0.062) in XR vs. NR. Although further study is needed, the findings suggest differential responses of this pathway may partially explain marked differences in rates of hypertrophy between XR and NR. Support: R01 AG017896 and VA Merit.