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Heat stress (HS) induces Akt/mTOR phosphorylation and FoxO3a signaling; however, whether a prior increase in heat shock protein 72 (HSP72) expression affects intracellular signaling following eccentric exercise remains unclear. We analyzed the effects of HS pretreatment on intramuscular signaling in response to acute exercise in 10‐week‐old male Wistar rats (n = 24). One leg of each rat was exposed to HS and the other served as an internal control (CT). Post‐HS, rats were either rested or subjected to downhill treadmill running. Intramuscular signaling responses in the red and white regions of the gastrocnemius muscle were analyzed before, immediately after, or 1 h after exercise (n = 8/group). HS significantly increased HSP72 levels in both deep red and superficial white regions. Although HS did not affect exercise‐induced mTOR signaling (S6K1/ERK) responses in the red region, mTOR phosphorylation in the white region was significantly higher in CT legs than in HS legs after exercise. Thr308 phosphorylation of Akt showed region‐specific alteration with a decrease in the red region and an increase in the white region immediately after downhill running. Overall, a prior increase in HSP72 expression elicits fiber type‐specific changes in exercise‐induced Akt and mTOR phosphorylation in rat gastrocnemius muscle. [ABSTRACT FROM AUTHOR]

Purpose: Physical activity (PA) is likely to be the most important modifiable factor in skeletal muscle development. However, the influence of PA on the skeletal muscle of preschool children has not been thoroughly investigated. The main objective of this study was to quantitatively measure PA, and then, to assess whether associations exist between site-specific muscle changes and PA in relation to sex and weight statuses in preschool children aged 3 to 4 years. Methods: A total of 86 healthy preschool children, aged 3–4 years, were instructed to wear an accelerometer for seven consecutive days. The number of steps taken daily, and minutes spent in moderate–vigorous PA (MVPA) and total PA (TPA) were recorded. Muscle thickness was measured by B-mode ultrasonography using a 5–18 MHz scanning head. Muscle thickness was measured at seven sites: the lateral forearm, upper arm, abdomen, anterior and posterior thigh, and anterior and posterior lower leg. Results: There was no significant difference between boys and girls in terms of MVPA and TPA on weekdays and weekends. According to the linear regression models, after adjusting for daylight duration, the muscle of the posterior thigh was significantly positively associated (p < 0.05) with daily steps and MVPA on weekdays for boys and girls, respectively. Conclusions: We found that the muscle thickness of the posterior thigh in preschool children was significantly positively associated with PA, as measured by daily steps and MVPA. We suggest that for the overall health and well-being of preschool children, the levels of PA should be maintained and/or increased, and preferably transformed into a regular part of daily living. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. Methods: By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). Results: The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13–0.67], [95% CI], and rmyosin = 0.83 [0.61–0.93], with p = 5.70 × 10–3 and 2.00 × 10–6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. Conclusions: This new method (https://github.com/OlaHanssonLab/PredictFiberType) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies. [ABSTRACT FROM AUTHOR]

Sakamoto, A, Naito, H, and Chow, CM. Hyperventilation-aided recovery for extra repetitions on bench press and leg press. J Strength Cond Res 34(5): 1274-1284, 2020-Hyperventilation (HV)-induced alkalosis, an ergogenic strategy, improved repeated pedaling sprint performance through enhanced H+ removal. However, it did not confer beneficial effects on other forms of exercises. This study investigated the benefits of HV-aided recovery on lifting repetitions and joint velocity during resistance training involving multiple joints and both concentric and eccentric contractions. Eleven power-trained men (mean ± SD age: 22.5 ± 4.3 years, training experience: 8.3±3.6 years) performed 6 sets each of bench press and leg press at 80% 1 repetition maximum. Each set was continued until failure, with a 5-minute recovery between sets. In protocol A, HV was implemented for 30 seconds before the first, third, and fifth sets of each exercise (HV-aided recovery), whereas spontaneous breathing continued throughout the recovery before the second, fourth, and sixth sets (control recovery). In protocol B, the order of the HV and control recoveries was reversed. For both protocols, reductions in repetitions (range: −4.7% to −22.5%) and velocity (range: −23.1% to −37.7%) were consistently observed after control recovery (p <0.05), whereas HV-aided recovery resulted in increased repetitions (range: +21.3% to +55.7%) and velocity (range: +6.3% to +15.3%) (p<0.05) or no reductions in these measures from the previous set. The total repetitions performed across 6 sets (protocols A and B combined) were greater after the HV-aided than control recovery (p ⩽ 0.001) in bench press (44±10 vs. 36±10 reps, increased by 27.1±24.1%) and leg press (64±9 vs. 50±15 reps, increased by 35.2 ± 29.5%). Hyperventilation-aided recovery may boost the effectiveness of resistance training through increased training volume and lifting velocity [ABSTRACT FROM AUTHOR]

Purpose: High-intensity neuromuscular electrical stimulation (NMES) training can induce muscle hypertrophy at the whole muscle and muscle fiber levels. However, whether low-intensity NMES training has a similar result is unknown. This study aimed to investigate whether low-intensity NMES training could elicit muscle hypertrophy at the whole muscle and muscle fiber levels in the human skeletal muscle.Methods: Eight untrained young males were subjected to 18 min of unilateral NMES training for 8 weeks. One leg received NMES at maximal tolerable intensity (HIGH); the other leg received NMES at an intensity half of that in the HIGH condition (LOW). Quadriceps muscle thickness (MT), muscle fiber cross-sectional area (CSA), and knee extension strength were measured before and after the training period.Results: The average training intensity throughout the intervention period in the HIGH and LOW conditions were 62.5 ± 4.6% maximal voluntary contraction (MVC) and 32.6 ± 2.6% MVC, respectively. MT, CSA, and muscle strength increased in both exercise conditions (p < 0.05); however, training effects in the LOW condition were lower than those in the HIGH condition (p < 0.05). The average training intensity showed a positive correlation with percent changes in muscle strength (r = 0.797, p = 0.001), MT (r = 0.876, p = 0.001), type I fiber CSA (r = 0.730, p = 0.01), and type II fiber CSA (r = 0.899, p = 0.001).Conclusions: Low-intensity NMES could increase MT, muscle fiber CSA, and muscle strength in healthy human skeletal muscles. However, the magnitude of increase is lower in low-intensity than in high-intensity NMES training. [ABSTRACT FROM AUTHOR]

Key points Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy., SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle., The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent., Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling., Abstract Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity ( P < 0.001). SIRT1-regulated Akt, endothelial nitric oxide synthase and GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased forkhead box O 1 (FOXO1) and increased K48 polyubiquitination also suggest that SIRT1 could be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1 and Nampt levels. Our results reveal a strong correlation between SIRT1 levels and activity, SIRT1-regulated pathways and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. [ABSTRACT FROM AUTHOR]

We examined the effect of repeated heat stress on muscle atrophy, and apoptotic and proteolytic regulation in unloaded rat slow- and fast-type skeletal muscles. Forty male Wistar rats (11 week-old) were divided into control ( CT), hindlimb unweighting ( HU), intermittent weight-bearing during HU ( HU + IWB), and intermittent weight-bearing with heat stress during HU (41-41.5°C for 30 min; HU + IWB + HS) groups. The HU + IWB + HS and HU + IWB groups were released from unloading for 1 h every second day, during which the HU + IWB + HS group underwent the heating. Our results revealed that repeated bouts of heat stress resulted in protection against disuse muscle atrophy in both soleus and plantaris muscles. This heat stress-induced protection against disuse-induced muscular atrophy may be partially due to reduced apoptotic activation in both muscles, and decreased ubiquitination in only the soleus muscle. We concluded that repeated heat stress attenuated skeletal muscle atrophy via suppressing apoptosis but the response to proteolytic systems depend on the muscle phenotype. [ABSTRACT FROM AUTHOR]

Purpose: Protein ingestion after resistance exercise increases muscle protein synthesis (MPS) in a dose-dependent manner. However, the molecular mechanism(s) for the dose-dependency of MPS remains unclear. This study aimed to determine the dose response of mammalian target of rapamycin (mTOR) signaling in muscle with ingestion of protein after resistance exercise. Methods: Fifteen male subjects performed four sets of six unilateral isokinetic concentric knee extensions. Immediately after exercise, eight subjects consumed water only. The other seven subjects, in a randomized-order crossover design, took either a 10 [3.6 g essential amino acids (EAA)] or 20 g (7.1 g EAA) solution of whey protein. Muscle biopsies from the vastus lateralis muscle were taken 30 min before and 1 h after resistance exercise. Phosphorylation of Akt (Ser473), mTOR (Ser2448), 4E-BP1 (Thr37/46), and S6K1 (Thr389) was measured by western blotting. Results: Concentric knee extension exercise alone did not increase phosphorylation of Akt and mTOR 1 h after exercise, but ingesting protein after exercise significantly increased the phosphorylation of Akt and mTOR in a dose-dependent manner ( P < 0.05). 4E-BP1 phosphorylation significantly decreased after resistance exercise ( P < 0.05), but subjects who took 10 or 20 g of protein after exercise showed increased 4E-BP1 from post-exercise dephosphorylation ( P < 0.05). S6K1 phosphorylation significantly increased after resistance exercise ( P < 0.05), and 20 g of protein further increased S6K1 phosphorylation compared with ingestion of 10 g ( P < 0.05). Conclusions: These findings suggest that whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in untrained men. [ABSTRACT FROM AUTHOR]

Human muscle fiber composition is heterogeneous and mainly determined by genetic factors. A previous study reported that experimentally induced iron deficiency in rats increases the proportion of fast-twitch muscle fibers. Iron status has been reported to be affected by genetic factors. As the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms are strongly associated with iron status in humans, we hypothesized that the genotype score (GS) based on these polymorphisms could be associated with the muscle fiber composition in humans. Herein, we examined 214 Japanese individuals, comprising of 107 men and 107 women, for possible associations of the GS for iron status with the proportion of myosin heavy chain (MHC) isoforms (I, IIa, and IIx) as markers of muscle fiber composition. No statistically significant correlations were found between the GS for iron status and the proportion of MHC isoforms in all participants. When the participants were stratified based on sex, women showed positive and negative correlations of the GS with MHC-IIa (age-adjusted p = 0.020) and MHC-IIx (age-adjusted p = 0.011), respectively. In contrast, no correlation was found in men. In women, a 1-point increase in the GS was associated with 2.42% higher MHC-IIa level and 2.72% lower MHC-IIx level. Our results suggest that the GS based on the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms for iron status is associated with muscle fiber composition in women. [ABSTRACT FROM AUTHOR]

Abstract: Skeletal muscle hosts all of the isoforms of nitric oxide synthase (NOS). It is well documented that nitric oxide (NO) regulates force generation and satellite cell activation, and therefore, damage repair of skeletal muscle. NO can also activate nociceptors of C-fibers, thereby causing the sensation of pain. Although delayed-onset of muscle soreness (DOMS) is associated with decreased maximal force generation, pain sensation and sarcomere damage, there is a paucity of research linking NO and DOMS. The present mini-review attempts to elucidate the possible relationship between NO and DOMS, based upon current literature. [Copyright &y& Elsevier]

Abstract: Alpha (α)-actinin-3 is located in the skeletal muscle Z-line and forms actin–actin crosslinks. An interesting property of α-actinin-3 is its expression pattern, which is restricted to fast type II skeletal muscle fibers. However, little is known about the response of α-actinin-3 levels to changes in skeletal muscle such as fiber type transformation. This study examined α-actinin-3 levels in the soleus muscles of rats subjected to hindlimb unloading, which causes a slow-to-fast fiber transformation in the soleus muscle. After unloading, type II myosin heavy chain (MyHC) and fast myosin levels increased significantly (P <0.0001 for type II MyHC, P <0.005 for fast myosin). Along with these increases in fast fibers, α-actinin-3 expression levels increased significantly (P <0.0007) and dramatically. These results indicate that α-actinin-3 levels increase concomitantly with increases in skeletal muscle fast fibers. [Copyright &y& Elsevier]

Protein kinase B [PKB, also known as Akt (PKB/Akt)] and calcineurin (CaN) are postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to disuse and increased muscle loading. These experiments investigated changes in signal transduction of the downstream pathways of PKB/Akt and CaN during recovery following disuse-induced muscle atrophy. A 10-day period of hindlimb unloading (HLU) via tail suspension (male rats) was used to produce soleus muscle atrophy. Muscle recovery was achieved by returning animals to normal ambulation for 3–10 days. HLU resulted in significant muscle atrophy and a slow-to-fast fiber transition as revealed by appearance of type IId/x and IIb myosin heavy chain (MHC) isoforms. Muscle mass in HLU animals recovered to control (Con) levels after 10 days of reloading, but the fast-to-slow shift in muscle MHC was incomplete, as indicated by the continued presence of type IId/x MHC. Ten days of HLU resulted in a significant decrease (-43%) in muscle levels of phosphorylated PKB/Akt. In contrast, muscle levels of phosphorylated PKB/Akt were greater (+56%) in HLU than in Con animals early after the onset of reloading (3 days). Soleus levels of phosphorylated p70s6K were significantly higher (+26%) in HLU animals after 3 days of muscle reloading. Muscle levels of phosphorylated PKB/Akt and phosphorylated p70s6K returned to Con levels by day 10 of recovery. Moreover, muscle CaN levels were significantly higher than Con levels after 10 days of muscle reloading. These findings are consistent with the hypothesis that PKB/Akt and its downstream mediators are active in the regrowth of muscle mass during the early periods of recovery from muscle atrophy. Our data support the concept that CaN is involved in muscle remodeling during the later phases of recovery from disuse muscle atrophy. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a highly plastic tissue. The role of heat shock protein 72 (Hsp72) in heat stress-induced skeletal muscle hypertrophy has been well demonstrated; however, the precise mechanisms remain unclear. Essential amino acids, such as leucine, mainly mediate muscle protein synthesis. We investigated the effects of pre-heating and increased Hsp72 expression on the mechanistic target of rapamycin (mTOR) signaling and protein synthesis following leucine administration in rat gastrocnemius muscle. To ensure increased Hsp72 expression in both the red and white portions of the muscle, one leg of male Wistar rats (10-week-old, n = 23) was heat-stressed in 43 °C water for 30 min twice at a 48-h-interval (heat-stressed leg, HS leg). The contralateral leg served as a non-heated internal control (CT leg). After the recovery period (48 h), rats were divided into the pre-administration or oral leucine administration groups. We harvested the gastrocnemius muscle (red and white parts) prior to administration and 30 and 90 min after leucine treatment (n = 7–8 per group) and intramuscular signaling responses to leucine ingestion were determined using western blotting. Heat stress significantly upregulated the expression of Hsp72 and was not altered by leucine administration. Although the phosphorylation levels of mTOR/S6K1 and ERK were similar regardless of heating, 4E-BP1 was less phosphorylated in the HS legs than the CT legs after leucine administration in the red portion of the muscles (P < 0.05). Moreover, c-Myc expression differed significantly after leucine administration in both the red and white portions of the muscles. Our findings indicate that following oral leucine administration, pre-heating partially blunted the muscle protein synthesis signaling response in the rat gastrocnemius muscle. • Pre-heating blunted muscle protein synthesis signaling response. • Hsp72 protein levels were not altered by leucine administration. • c-Myc expression was higher in CT than in HS legs after leucine administration. [ABSTRACT FROM AUTHOR]

Human skeletal muscle fiber is heterogenous due to its diversity of slow- and fast-twitch fibers. In human, slow-twitched fiber gene expression is correlated to MOTS-c, a mitochondria-derived peptide that has been characterized as an exercise mimetic. Within the MOTS-c open reading frame, there is an East Asian-specific m.1382A>C polymorphism (rs111033358) that changes the 14th amino acid of MOTS-c (i.e., K14Q), a variant of MOTS-c that has less biological activity. Here, we examined the influence of the m.1382A>C polymorphism causing MOTS-c K14Q on skeletal muscle fiber composition and physical performance. The myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx) as an indicator of muscle fiber composition were assessed in 211 Japanese healthy individuals (102 men and 109 women). Muscular strength was measured in 86 physically active young Japanese men by using an isokinetic dynamometer. The allele frequency of the m.1382A>C polymorphism was assessed in 721 Japanese athletes and 873 ethnicity-matched controls. The m.1382A>C polymorphism genotype was analyzed by TaqMan SNP Genotyping Assay. Individuals with the C allele of the m.1382A>C exhibited a higher proportion of MHC-IIx, an index of fast-twitched fiber, than the A allele carriers. Men with the C allele of m.1382A>C exhibited significantly higher peak torques of leg flexion and extension. Furthermore, the C allele frequency was higher in the order of sprint/power athletes (6.5%), controls (5.1%), and endurance athletes (2.9%). Additionally, young male mice were injected with the MOTS-c neutralizing antibody once a week for four weeks to mimic the C allele of the m.1382A>C and assessed for protein expression levels of MHC-fast and MHC-slow. Mice injected with MOTS-c neutralizing antibody showed a higher expression of MHC-fast than the control mice. These results suggest that the C allele of the East Asian-specific m.1382A>C polymorphism leads to the MOTS-c K14Q contributes to the sprint/power performance through regulating skeletal muscle fiber composition. • There is an East Asian-specific m.1382A>C polymorphism in the mtDNA that changes the 14th amino acid of MOTS-c (i.e., K14Q). • C allele of the MOTS-c m.1382A>C showed a higher percentage of MHC-IIx and muscular strength than the A allele. • C allele frequency of the MOTS-c m.1382A>C polymorphism overrepresented in the sprint/power athletes. • MOTS-c neutralizing, mimicking C allele, showed lower and higher expression of MHC-slow and -fast than controls. [ABSTRACT FROM AUTHOR]

Changes in histone acetylation and methylation status with aging affect gene expression and phenotype in several tissues; however, age-related changes in histone modification in the skeletal muscle have not been elucidated yet. This study investigated age-related global changes in histone modification in rat gastrocnemius muscle. Male Wistar rats (n = 28) were assigned to one of four age groups (n = 7 per group) corresponding to different life stages: 3 months old (3-mo; young), 6 months old (adult), 12 months old (12-mo; middle-aged), and 24 months old (24-mo; old). The gastrocnemius muscle was removed and global histone modification (acetylation and tri-methylation) at K9 and K27 was evaluated by western blotting. Relative muscle mass decreased in the 12- and 24-mo rats accompanied with reduction in type IIb myosin heavy chain isoforms and Myh4 (MHC IIB) mRNA expression. Histone H3 acetylation decreased in an age-dependent manner, with lower levels in 12- and 24-mo groups than in the 3-mo group. K9 and K27 acetylation decreased with age. Although there was no significant change in K27 tri-methylation, K9 tri-methylation showed an age-dependent decline. Histone modification status (acetylation at K9 and K27 and tri-methylation at K9) was positively associated with relative gastrocnemius muscle weight, the percentage of type IIb myosin heavy chain isoform, myosin heavy chain type IIb protein expression, and the level of Myh4 mRNA. Thus, global histone H3 methylation and acetylation decrease with age, and the latter might be associated with age-related muscle atrophy of rat gastrocnemius muscle. • Global histone H3 methylation and acetylation decrease with age. • SIRT1 accumulation in nuclei presumably could induce H3K9 and H3K27 deacetylation. • Changes may be linked to age-related type IIb fiber atrophy in rat skeletal muscle. [ABSTRACT FROM AUTHOR]