ABSTRACT
ABSTRACT: de Lemos Muller, CH, Farinha, JB, Leal-Menezes, R, and Ramis, TR. Aerobic training with blood flow restriction on muscle hypertrophy and strength: systematic review and meta-analysis. J Strength Cond Res 38(7): 1341-1349, 2024-Integrating strength and endurance training in a single exercise session, even on separate days, can be physically demanding and time-consuming. Therefore, there is a growing interest in identifying efficient training methods that can concurrently enhance cardiovascular and neuromuscular performance through a singular training modality. This study conducted a systematic review and meta-analysis to explore the effects of aerobic training with blood flow restriction (AT + BFR) on muscle hypertrophy and strength gains in healthy individuals. Our study was registered at PROSPERO and used multiple databases (PubMed, Embase, Scopus, and Web of Science), seeking clinical trials that examined AT + BFR influence on muscle hypertrophy and strength gains in individuals aged 18-60 years and comparing with aerobic training without BFR. The risk of bias and method quality were assessed using the ROB2.0 tool and PEDro scale, respectively, and the quality of evidence was evaluated with the GRADE method. A random-effects model was used for meta-analysis, and standardized mean difference (SMD) was calculated for each outcome. Of 4,462 records, 29 full texts were assessed for eligibility, with 7 articles meeting the inclusion criteria. The results indicated that AT + BFR was more beneficial for inducing muscle hypertrophy than aerobic training without BFR (SMD [95% CI] = 0.86 [0.37-1.35]; I2 = 42%). Furthermore, AT + BFR was associated with greater improvements in muscle strength (SMD [95% CI] = 0.41 [0.10-0.72]; I2 = 0%). Despite the generally high risk of bias for both outcomes, these encouraging findings underscore the clinical significance of AT + BFR as a compelling tool for enhancing neuromuscular parameters.
Subject(s)
Muscle Strength , Muscle, Skeletal , Resistance Training , Humans , Muscle Strength/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/blood supply , Resistance Training/methods , Exercise/physiology , Hypertrophy , Blood Flow Restriction Therapy , Regional Blood Flow/physiology , Skeletal Muscle EnlargementABSTRACT
Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that macrophages could also present two major subsets during tissue healing: proliferative macrophages (M1-like), which are responsible for increasing myogenic cell proliferation, and restorative macrophages (M2-like), which are involved in the end of the mature muscle myogenesis. The participation and characterization of these macrophage subsets are critical during myogenesis to understand the inflammatory role of macrophages during muscle recovery and to create supportive strategies that can improve mass muscle maintenance. Indeed, most of our knowledge about macrophage subsets comes from skeletal muscle damage protocols, and we still do not know how these subsets can contribute to skeletal muscle adaptation. Thus, this narrative review aims to collect and discuss studies demonstrating the involvement of different macrophage subsets during the skeletal muscle damage/regeneration process, showcasing an essential role of these macrophage subsets during muscle adaptation induced by acute and chronic exercise programs.
Subject(s)
Cell Proliferation , Exercise , Hypertrophy/metabolism , Inflammation Mediators/metabolism , Inflammation/metabolism , Macrophages/metabolism , Muscle, Skeletal/metabolism , Regeneration , Skeletal Muscle Enlargement , Animals , Humans , Hypertrophy/immunology , Hypertrophy/pathology , Hypertrophy/physiopathology , Inflammation/immunology , Inflammation/pathology , Inflammation/physiopathology , Macrophages/immunology , Muscle, Skeletal/immunology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Phenotype , Signal TransductionABSTRACT
The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as 1) predictive of hypertrophy, 2) responsive to RT independent of muscle hypertrophy, or 3) plastic with hypertrophy. Older adults (n = 31, 18 F/13 M, 70 ± 4 yr) underwent 14-wk RT (3 days/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome] and thigh lean mass [dual-energy X-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n = 31) and post-RT (n = 22). Prediction networks (using only baseline RNA-seq) were identified by weighted gene correlation network analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-level information extractor (PLIER) was applied to identify Response networks and link genes to biological annotation. Prediction networks (n = 6) confirmed transcripts previously connected to resistance/aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n = 6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that interindividual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity. Code/Data: https://github.com/kallavin/MASTERS_manuscript/tree/master.
Subject(s)
Gene Regulatory Networks , Resistance Training , Skeletal Muscle Enlargement/genetics , Absorptiometry, Photon , Aged , Female , Humans , Male , Muscle, Skeletal/physiologyABSTRACT
Resistance exercises eliciting eccentric overload (EO) are considered to strongly promote muscular hypertrophy and broad neuromuscular adaptations but typically require specialized equipment. The aims of these experiments were to assess whether EO is achieved during common high-speed stretch-shortening cycle (SSC) exercises (rebound bench press throw [RBPT] and squat jump [SJ]), and to test the effect of the external load on the EO achieved. Twenty-nine under 18 handball players and fifteen physically active males (24.9 ± 3.2 years) took part in the experiments. Testing consisted of a single set of 6 repetitions with light (25%-30% 1-RM), moderate (50% 1-RM), and heavy (70%-75% 1-RM) loads. Eccentric and concentric force near the zero-velocity point (50-200 ms) as well as eccentric-concentric force ratio (EO; %) were calculated. In RBPT, higher EO values were found at 50% 1-RM than 70% 1-RM in the time interval 50 ms before and after the zero-velocity point. Higher EO values were also found at 50% 1-RM than both 30% 1-RM and 70% 1-RM 100 ms before and after the zero-velocity point. For the SJ, higher EO values were found at 50% 1-RM and 75% 1-RM than 25% 1-RM 100 ms before and after the zero-velocity point. Higher EO values were found at 50% 1-RM than 25% 1-RM 200 ms before and after the zero-velocity point. However, the higher EO values in the SJ were found far from the zero-velocity point. High-speed SSC resistance training provides similar EO to other methods and thus should promote muscle hypertrophy and other neuromuscular adaptations.
Subject(s)
Adaptation, Physiological , Muscle Strength , Resistance Training/methods , Skeletal Muscle Enlargement , Adolescent , Adult , Biomechanical Phenomena , Exercise Test , Humans , Male , Muscle Contraction , Weight Lifting/physiology , Young AdultABSTRACT
Strength training promotes a IIX-to-IIA shift in myosin heavy chain (MHC) composition, likely due to changes in sarcoplasmic [Ca2+ ] which are sensed by CaMKII. Sarcoplasmic [Ca2+ ] is in part regulated by sarcolipin (SLN), a small protein that when overexpressed in rodents stimulates mitochondrial biogenesis and a fast-to-slow fiber type shift. The purpose of this study was to determine whether CaMKII and SLN are involved in muscle phenotype and performance changes elicited by strength training. Twenty-two men followed an 8-week velocity-based resistance training program using the full squat exercise while monitoring repetition velocity. Subjects were randomly assigned to two resistance training programs differing in the repetition velocity loss allowed in each set: 20% (VL20) vs 40% (VL40). Strength training caused muscle hypertrophy, improved 1RM and increased total CaMKII protein expression, particularly of the δD isoform. Phospho-Thr287 -CaMKII δD expression increased only in VL40 (+89%), which experienced greater muscle hypertrophy, and a reduction in MHC-IIX percentage. SLN expression was increased in VL20 (+33%) remaining unaltered in VL40. The changes in phospho-Thr287 -CaMKII δD were positively associated with muscle hypertrophy and the number of repetitions during training, and negatively with the changes in MHC-IIX and SLN. Most OXPHOS proteins remained unchanged, except for NDUFB8 (Complex I), which was reduced after training (-22%) in both groups. The amount of fatigue allowed in each set critically influences muscle CaMKII and SLN responses and determines muscle phenotype changes. With lower intra-set fatigue, the IIX-to-IIA MHC shift is attenuated.
Subject(s)
Muscle Fatigue , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Proteolipids/metabolism , Resistance Training/methods , Adaptation, Physiological , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Humans , Male , Mitochondria, Muscle/metabolism , Mitochondrial Proteins/biosynthesis , Myosin Heavy Chains/metabolism , Phosphorylation , Skeletal Muscle EnlargementABSTRACT
The purpose was to compare the effects of protein (whey protein) and carbohydrate supplementation and protein alone both combined with resistance training on muscle strength, muscle mass and total training volume progression in untrained young men. Resistance training was performed using the leg press and knee extension until concentric failure (8-12 repetition maximum), three times a week for eight weeks. Muscle strength and muscle cross-sectional area were assessed before and after training. Total training volume progression was calculated considering the first and eighth week. Seventeen men completed the study (protein and carbohydrate, n=9, age 23.44 ± 4.56 years, weight: 62.13±6.17 kg, height: 1.75±0.02 m, body mass index: 20.29±2.08 kg/m2; protein, n=8, age 24.63±2.39 years, weight: 69.01±5.57 kg, height: 1.77±0.07 m; body mass index: 21.64±1.05 kg/m2. Both protocols showed similar increases in muscle strength (effect size: protein and carbohydrate=1.28; protein=0.97; p<0.001), muscle cross sectional area (effect size: protein and carbohydrate=0.66; protein=0.47; p<0.001) and total training volume progression (effect size: protein and carbohydrate=2.68; protein=1.63; p<0.001) after training. No differences were found between groups p>0.05). Protein and carbohydrate supplementation combined with resistance training does not induce greater gains in muscle strength, hypertrophy and total training volume compared to resistance training combined with protein alone in untrained individuals.
Subject(s)
Adaptation, Physiological , Dietary Carbohydrates/administration & dosage , Dietary Supplements , Muscle, Skeletal/physiology , Resistance Training/methods , Whey Proteins/administration & dosage , Adolescent , Adult , Humans , Knee/physiology , Leg/physiology , Male , Muscle Strength , Muscle, Skeletal/anatomy & histology , Skeletal Muscle Enlargement , Young AdultABSTRACT
Resistance training is a commonly used strategy for improving both athletic performance and general health. While the contribution of resistance training intensity and volume to muscle strength and hypertrophy have been extensively investigated, training frequency only recently received sufficient attention, especially in older adults. A meta-regression was conducted to compare muscle strength and hypertrophic adaptations to resistance training programmes performed with different training frequencies in adults over 60 years of age. The systematic literature search identified 14 articles for meta-regression. For each outcome, an effect size (ES) was calculated as the pre-test-post-test change, divided by the pooled pre-test standard deviation (SD). Random-effects meta-regressions for multilevel data structures, using study as the clustering variable, were performed using package metafor in R. Maximal strength shows a significant effect of frequency (p = 0.001), with an increase in effect size of 0.14 for every day increase in frequency (CI: 0.08, 0.21). For muscle hypertrophy, no significant effect of frequency was found (p = 0.67). Considering that muscle hypertrophy was not affected, while maximum strength was only slightly improved with additional training days, it seems unlikely that more than two weekly resistance training sessions would provide any further benefits for older adults.
Subject(s)
Aging/physiology , Muscle Strength , Resistance Training/methods , Skeletal Muscle Enlargement , Adaptation, Physiological , Humans , Middle Aged , Regression Analysis , Time FactorsABSTRACT
This systematic review and meta-analysis determined resistance training (RT) load effects on various muscle hypertrophy, strength, and neuromuscular performance task [e.g., countermovement jump (CMJ)] outcomes. Relevent studies comparing higher-load [>60% 1-repetition maximum (RM) or <15-RM] and lower-load (≤60% 1-RM or ≥ 15-RM) RT were identified, with 45 studies (from 4713 total) included in the meta-analysis. Higher- and lower-load RT induced similar muscle hypertrophy at the whole-body (lean/fat-free mass; [ES (95% CI) = 0.05 (-0.20 to 0.29), P = 0.70]), whole-muscle [ES = 0.06 (-0.11 to 0.24), P = 0.47], and muscle fibre [ES = 0.29 (-0.09 to 0.66), P = 0.13] levels. Higher-load RT further improved 1-RM [ES = 0.34 (0.15 to 0.52), P = 0.0003] and isometric [ES = 0.41 (0.07 to 0.76), P = 0.02] strength. The superiority of higher-load RT on 1-RM strength was greater in younger [ES = 0.34 (0.12 to 0.55), P = 0.002] versus older [ES = 0.20 (-0.00 to 0.41), P = 0.05] participants. Higher- and lower-load RT therefore induce similar muscle hypertrophy (at multiple physiological levels), while higher-load RT elicits superior 1-RM and isometric strength. The influence of RT loads on neuromuscular task performance is however unclear.
Subject(s)
Muscle Strength/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Resistance Training/methods , Skeletal Muscle Enlargement/physiology , Age Factors , Body Mass Index , Humans , Isometric Contraction , Muscle Fibers, Skeletal/physiology , Perception/physiology , Physical Exertion/physiology , Task Performance and AnalysisABSTRACT
There is emerging evidence suggesting that muscle growth is not homogeneous through the muscle. The aim of the present study was to analyse the role of exercise selection in regional hypertrophy. Two randomly allocated groups with equal training volume and intensity performed squats in the smith machine (SMTH group) or the leg extension exercise (LEG group). Growth in proximal, central and distal regions of the rectus femoris (RF) and vastus lateralis (VL) muscles, jump height and body composition were analysed. Results show that the three regions of RF grew significantly in the participants of the LEG group (p < 0.05), while only the central region of VL grew significantly in the SMTH group (p < 0.05). In summary, this study confirms that exercise selection plays a role in regional hypertrophy. Whilst there may be still other factors that determine how muscles grow, it seems that the chosen exercises may be responsible of the differences observed in this study.
Subject(s)
Exercise/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Resistance Training/methods , Skeletal Muscle Enlargement/physiology , Adaptation, Physiological , Adult , Anthropometry , Hip/physiology , Humans , Leg/physiology , Male , Young AdultABSTRACT
Cannabidiol (CBD) has proven clinical benefits in the treatment of seizures, inflammation, and pain. The recent legalization of CBD in many countries has caused increased interest in the drug as an over-the-counter treatment for athletes looking to improve recovery. However, no data on the effects of CBD on the adaptive response to exercise in muscle are available. To address this gap, we eccentrically loaded the tibialis anterior muscle of 14 rats, injected them with a vehicle (n = 7) or 100 mg/kg CBD (n = 7), and measured markers of injury, inflammation, anabolic signaling, and autophagy 18 hr later. Pro-inflammatory signaling through nuclear factor kappa B (NF-kB) (Ser536) increased with loading in both groups; however, the effect was significantly greater (36%) in the vehicle group (p < .05). Simultaneously, anabolic signaling through ribosomal protein S6 kinase beta-1 (S6K1) (Thr389) increased after eccentric contractions in both groups with no difference between vehicle and CBD (p = .66). The ribosomal protein S6 phosphorylation (240/244) increased with stimulation (p < .001) and tended to be higher in the CBD group (p = .09). The ubiquitin-binding protein p62 levels were not modulated by stimulation (p = .6), but they were 46% greater in the CBD compared with the vehicle group (p = .01). Although liver weight did not differ between the groups (p = .99) and levels of proteins associated with stress were similar, we did observe serious side effects in one animal. In conclusion, an acute dose of CBD decreased pro-inflammatory signaling in the tibialis anterior without blunting the anabolic response to exercise in rats. Future research should determine whether these effects translate to improved recovery without altering adaptation in humans.
Subject(s)
Cannabidiol/pharmacology , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Physical Conditioning, Animal/physiology , Animals , Anti-Inflammatory Agents/pharmacology , Autophagy , Cannabidiol/toxicity , Electric Stimulation , Female , Liver/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Organ Size/drug effects , Phosphorylation , Protein Structural Elements/drug effects , Rats, Sprague-Dawley , Sciatic Nerve , Signal Transduction/drug effects , Skeletal Muscle Enlargement/drug effectsABSTRACT
PURPOSE: This study aimed to analyze the effect of resistance training (RT) performed until volitional failure with low, moderate, and high loads on muscle hypertrophy and muscle strength in healthy adults and to assess the possible participant-, design-, and training-related covariates that may affect the adaptations. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases were searched. Including only studies that performed sets to volitional failure, the effects of low- (>15 repetitions maximum (RM)), moderate- (9-15 RM), and high-load (≤8 RM) RTs were examined in healthy adults. Network meta-analysis was undertaken to calculate the standardized mean difference (SMD) between RT loads in overall and subgroup analyses involving studies deemed of high quality. Associations between participant-, design-, and training-related covariates with SMD were assessed by univariate and multivariate network meta-regression analyses. RESULTS: Twenty-eight studies involving 747 healthy adults were included. Although no differences in muscle hypertrophy between RT loads were found in overall (P = 0.113-0.469) or subgroup analysis (P = 0.871-0.995), greater effects were observed in untrained participants (P = 0.033) and participants with some training background who undertook more RT sessions (P = 0.031-0.045). Muscle strength improvement was superior for both high-load and moderate-load compared with low-load RT in overall and subgroup analysis (SMD, 0.60-0.63 and 0.34-0.35, respectively; P < 0.001-0.003), with a nonsignificant but superior effect for high compared with moderate load (SMD, 0.26-0.28, P = 0.068). CONCLUSIONS: Although muscle hypertrophy improvements seem to be load independent, increases in muscle strength are superior in high-load RT programs. Untrained participants exhibit greater muscle hypertrophy, whereas undertaking more RT sessions provides superior gains in those with previous training experience.
Subject(s)
Muscle Strength , Resistance Training/methods , Skeletal Muscle Enlargement , Adult , Female , Humans , Male , Network Meta-AnalysisABSTRACT
This paper aimed to compare the effect of drop-set (DS) and rest-pause (RP) systems versus traditional resistance training (TRT) with equalized total training volume on maximum dynamic strength (1RM) and thigh muscle thickness (MT). Twenty-eight resistance-trained males were randomly assigned to either RP (n = 10), DS (n = 9) or TRT (n = 9) protocols performed twice a week for 8 weeks. 1RM and MT of the proximal, middle and distal portions of the lateral thigh were assessed at baseline and post-intervention. A significant time × group interaction was observed for 1RM (P = 0.001) in the barbell back squat after 8-weeks. Post hoc comparisons revealed that RP promoted higher 1RM than TRT (P = 0.001); no statistical differences in strength were observed between the other conditions. A significant main effect of time was revealed for MT at the proximal (P = 0.0001) and middle (P = 0.0001) aspects of the lateral thigh for all training groups; however, the distal portion did not show a time effect (P = 0.190). There were no between-group interactions for MT. Our findings suggest that RP promotes slightly superior strength-related improvements compared with TRT, but hypertrophic adaptations are similar between conditions. Novelty: Rest-pause elicited a slightly superior benefit for strength adaptations compared with traditional resistance training. Resistance training systems do not promote superior hypertrophic adaptations when total training volume is equalized. Muscle thickness in distal portion of thigh is similar to baseline. Although modest, effect sizes tended to favor rest-pause.
Subject(s)
Adaptation, Physiological , Muscle Strength/physiology , Resistance Training/methods , Skeletal Muscle Enlargement , Adult , Diet Records , Humans , Male , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Rest , Thigh/anatomy & histology , Young AdultABSTRACT
Menopause transition may impair muscle function, decreasing exercise tolerance. The torque-duration relationship (hyperbolic curve) forms a practical framework within which exercise tolerance may be explored. In this regard, resistance training (RT) increases the curvature constant of this relationship (W'). Muscle hypertrophy and strength gains have been suggested as possible mediators of RT-induced improvement in W', however, it is unclear what the main mediator is. Higher-volume RT (HV-RT), beyond that recommended by RT-guidelines (i.e. three sets per exercise), may promote greater hypertrophy, but not higher strength gains. Hence, this study aimed to investigate whether greater hypertrophy in HV-RT maximises W' gain when compared to LVRT in postmenopausal women (PW). Fifty-eight PW were randomised to the control group (CTRL), HV-RT (six sets per exercise) or LV-RT (three sets per exercise). They underwent a 12-week RT program and were assessed for W', thigh lean body mass (TLBM) and maximal isometric voluntary contraction (MIVC). The TLBM gain was higher (P < 0.001) in the HV-RT (9.4%) than LV-RT (3.7%). However, both HV-RT and LV-RT similarly increased MIVC (9.7% vs. 16.5%, P = 0.063) and W' (26.4% vs. 34.6% P = 0.163). Additionally, the changes in W' were associated with the changes in TLBM (31%, P = 0.003) and MIVC (52%, P= <0.001). However, when the changes in TLBM and MIVC were inserted into the predictive model, only the MIVC (33%, P = 0.002) was a predictor of W'. Thus, although HV-RT promoted greater hypertrophy than LV-RT, HV-RT does not seem to maximise W' in PW.
Subject(s)
Exercise Tolerance , Muscle Strength , Muscle, Skeletal/anatomy & histology , Postmenopause/physiology , Resistance Training , Skeletal Muscle Enlargement , Body Mass Index , Female , Humans , Isometric Contraction , Middle Aged , Muscle, Skeletal/physiology , Resistance Training/methodsABSTRACT
Mechanical signals, such as those evoked by maximal-intensity contractions (MICs), can induce an increase in muscle mass. Rapamycin-sensitive signaling events are widely implicated in the regulation of this process; however, recent studies indicate that rapamycin-insensitive signaling events are also involved. Thus, to identify these events, we generate a map of the MIC-regulated and rapamycin-sensitive phosphoproteome. In total, we quantify more than 10,000 unique phosphorylation sites and find that more than 2,000 of these sites are significantly affected by MICs, but remarkably, only 38 of the MIC-regulated events are mediated through a rapamycin-sensitive mechanism. Further interrogation of the rapamycin-insensitive phosphorylation events identifies the S473 residue on Tripartite Motif-Containing 28 (TRIM28) as one of the most robust MIC-regulated phosphorylation sites, and extensive follow-up studies suggest that TRIM28 significantly contributes to the homeostatic regulation of muscle size and function as well as the hypertrophy that occurs in response to increased mechanical loading.
Subject(s)
Muscle Contraction , Muscle, Skeletal/metabolism , Proteome , Proteomics , TOR Serine-Threonine Kinases/metabolism , Tripartite Motif-Containing Protein 28/metabolism , Animals , Glycolysis , Hypertrophy , MTOR Inhibitors/pharmacology , Male , Mechanotransduction, Cellular , Mice, Inbred C57BL , Mice, Knockout , Muscle, Skeletal/drug effects , Phosphorylation , Sirolimus/pharmacology , Skeletal Muscle Enlargement , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/genetics , Tripartite Motif-Containing Protein 28/geneticsABSTRACT
Muscle differentiation is a multifaceted and tightly controlled process required for the formation of skeletal muscle fibers. Satellite cells are the direct cellular contributors to muscle repair in injuries or disorders. Here, we show that autotaxin (Atx) expression and activity is required for satellite cell differentiation. Conditional ablation of Atx or its pharmacological inhibition impairs muscle repair. Mechanistically, we identify LPAR1 as the key receptor in Atx-LPA signaling. Myogenic gene array and pathway analysis identified that Atx-LPA signaling activates ribosomal protein S6 kinase (S6K), an mTOR-dependent master regulator of muscle cell growth via LPAR1. Furthermore, Atx transgenic mice show muscle hypertrophic effects and accelerated regeneration. Intramuscular injections of Atx/LPA show muscle hypertrophy. In addition, the regulatory effects of Atx on differentiation are conserved in human myoblasts. This study identifies Atx as a critical master regulator in murine and human muscles, identifying a promising extracellular ligand in muscle formation, regeneration, and hypertrophy.
Subject(s)
Lysophospholipids/metabolism , Muscle Development , Muscle, Skeletal/metabolism , Phosphoric Diester Hydrolases/metabolism , Receptors, Lysophosphatidic Acid/metabolism , Regeneration , Satellite Cells, Skeletal Muscle/metabolism , Animals , Cell Line , Female , Gene Expression Regulation , Humans , Hypertrophy , Male , Mice, Inbred C57BL , Mice, Knockout , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Phosphoric Diester Hydrolases/genetics , Receptors, Lysophosphatidic Acid/genetics , Ribosomal Protein S6 Kinases/metabolism , Satellite Cells, Skeletal Muscle/pathology , Signal Transduction , Skeletal Muscle Enlargement , TOR Serine-Threonine Kinases/metabolismABSTRACT
Fucoidan is a sulfated polysaccharide found in a range of brown algae species. Growing evidence supports the long-term supplementation of fucoidan as an ergogenic aid to improve skeletal muscle performance. The aim of this study was to investigate the effect of fucoidan on the skeletal muscle of mice. Male BL/6 mice (N = 8-10) were administered a novel fucoidan blend (FUC, 400 mg/kg/day) or vehicle (CON) for 4 weeks. Treatment and control experimental groups were further separated into exercise (CON+EX, FUC+EX) or no-exercise (CON, FUC) groups, where exercised groups performed 30 min of treadmill training three times per week. At the completion of the 4-week treatment period, there was a significant increase in cross-sectional area (CSA) of muscle fibers in fucoidan-treated extensor digitorum longus (EDL) and soleus fibers, which was accompanied by a significant increase in tibialis anterior (TA) muscle force production in fucoidan-treated groups. There were no significant changes in grip strength or treadmill time to fatigue, nor was there an effect of fucoidan or exercise on mass of TA, EDL, or soleus muscles. In gastrocnemius muscles, there was no change in mRNA expression of mitochondrial biogenesis markers PGC-1α and Nrf-2 in any experimental groups; however, there was a significant effect of fucoidan supplementation on myosin heavy chain (MHC)-2x, but not MHC-2a, mRNA expression. Overall, fucoidan increased muscle size and strength after 4 weeks of supplementation in both exercised and no-exercised mice suggesting an important influence of fucoidan on skeletal muscle physiology.
Subject(s)
Anabolic Agents/administration & dosage , Muscle Contraction/drug effects , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Physical Endurance/drug effects , Polysaccharides/administration & dosage , Skeletal Muscle Enlargement/drug effects , Administration, Oral , Animals , Male , Mice, Inbred C57BL , Mitochondria, Muscle/drug effects , Mitochondria, Muscle/genetics , Mitochondria, Muscle/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Muscle, Skeletal/metabolism , Time FactorsABSTRACT
The optimal pattern of sedentarism displacement and mechanisms underlying its health effects are poorly understood. Therefore, the aim of this study was to quantify muscle-tendon adaptation in response to two different sedentarism displacement interventions and relate any adaptations to functional outcomes. Thirty-four older women (73±5yrs) underwent skeletal muscle-tendon size and functional assessments. Participants were randomly allocated to: Sedentary behavior fragmentation (SBF), Light intensity physical activity (LIPA), or Control groups. Measures were taken at weeks 0 and 8. Gait speed significantly increased (p=0.003), in both experimental groups (SBF: 0.06 ± 0.08m/s, 6±10%, LIPA: 0.06 ± 0.07m/s, 6±6%), but not control (-0.02 ± 0.12m/s, -2±9%). Accordingly, the relative change in Vastus Lateralis muscle volume, accounted for 30% (p=0.027), and 45% (p=0.0006) of the explained variance in the relative change in gait speed, for SBF and LIPA respectively. Gastrocnemius Medialis fascicle length changes were positively associated with gait speed changes, following LIPA exclusively (R2= 0.50, p=0.009). This is the first study to show SBF and LIPA are adequate loading in older women, with related muscle adaptation and clinically relevant gait speed improvements. Such adaptations appear similar irrespective of whether sedentarism displacement is prescribed in a single bout (LIPA) or in frequent micro-bouts (SBF).
Subject(s)
Exercise , Quadriceps Muscle/growth & development , Sedentary Behavior , Skeletal Muscle Enlargement , Adaptation, Physiological , Age Factors , Aged , Body Composition , England , Female , Functional Status , Health Behavior , Humans , Quadriceps Muscle/diagnostic imaging , Sex Factors , Walking SpeedABSTRACT
BACKGROUND: Most papers examining the lateral abdominal muscles (LAMs) and low back pain (LBP) are cross-sectional, with groups of participants being divided into a control and an LBP group. We hypothesized that morphological measurements of the LAMs in adolescent soccer players may predict future LBP incidence. The aim of this study was to examine the associations between the morphology of LAMs and LBP incidence rate among adolescent soccer players. METHODS: Ninety-seven adolescent male soccer players with no LBP at baseline were recruited into the prospective cohort study. The thickness of the LAMs was measured at baseline by ultrasound imaging in a supine rest position. Nine cases of LBP occurred during the follow-up 6-month observation. RESULTS: An obliquus internus (OI) asymmetry was related to increasing LBP risk (odds ratioâ¯=â¯19.99; 95%CI: 2.4-167.9). Spearman correlation also showed a linear relationship between OI asymmetry value and duration of LBP (Râ¯=â¯0.75, pâ¯=â¯0.02). An OI side-to-side difference greater than 1.25â¯mm suggests possible LBP incidence in the 6-month observation among adolescent soccer players. CONCLUSION: The morphological changes of the OI may be related to LBP's incidence in adolescent soccer players. The presence of OI asymmetry increases the odds of LBP by at least 2.4 times. Hypertrophy of the OI on one side of the body may contribute to trunk muscle imbalance.
Subject(s)
Abdominal Muscles/anatomy & histology , Low Back Pain/etiology , Soccer/physiology , Abdominal Muscles/diagnostic imaging , Abdominal Oblique Muscles/anatomy & histology , Abdominal Oblique Muscles/diagnostic imaging , Adolescent , Child , Humans , Longitudinal Studies , Low Back Pain/diagnostic imaging , Male , Prospective Studies , Skeletal Muscle Enlargement , UltrasonographyABSTRACT
Evidence from clinical trials and observational studies suggests that both progressive resistance exercise training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response. To understand potential mechanisms underlying the inhibitory effect of metformin on PRT, we analyzed the muscle transcriptome in 23 metPRT and 24 plaPRT participants. PRT significantly increased expression of genes involved in extracellular matrix remodeling pathways, and downregulated RNA processing pathways in both groups, however, metformin attenuated the number of differentially expressed genes within these pathways compared to plaPRT. Pathway analysis showed that genes unique to metPRT modulated aging-relevant pathways, such as cellular senescence and autophagy. Differentially expressed genes from baseline biopsies in older adults compared to resting muscle from young volunteers were reduced following PRT in plaPRT and were further reduced in metPRT. We suggest that although metformin may blunt pathways induced by PRT to promote muscle hypertrophy, adjunctive metformin during PRT may have beneficial effects on aging-associated pathways in muscle from older adults.
Subject(s)
Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Quadriceps Muscle/drug effects , Resistance Training , Skeletal Muscle Enlargement/drug effects , Transcriptome/drug effects , Adaptation, Physiological , Aged , Alabama , Double-Blind Method , Female , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Humans , Kentucky , Male , Quadriceps Muscle/growth & development , Quadriceps Muscle/metabolism , Time Factors , Treatment OutcomeABSTRACT
MiR-33a is found as a regulator of cell proliferation in many cancer cells. However, it remains unknown if and how miR-33a plays a role in myoblast proliferation. To investigate the effect of miR-33a on myoblast proliferation, miR-33a mimic or inhibitor was co-administered with or without insulin-like growth factor 1 (IGF1) to simulation myoblasts. Our study showed that up-regulation of miR-33a impaired myoblast proliferation, while down-regulation of miR-33a enhanced myoblast proliferation. Mechanistically, we examined that miR-33a can inhibit the transcription of IGF1, follistatin (FST) and cyclin D1 (CCND1) by targeting their 3'UTR region in both HEK293T cells and duck myoblasts. Moreover, up-regulation of miR-33a decreased and its down-regulation increased the mRNA expression of PI3K, Akt, mTOR and S6K. Importantly, the decreased PI3K, Akt, mTOR and S6K expression by miR-33a mimics was abrogated by co-administered with IGF1. Altogether, our results demonstrated that miR-33a may directly target IGF1, FST and CCND1 to inhibit myoblast proliferation via PI3K/Akt/mTOR signaling pathway. In conclusion, miR-33a is a potential negative regulator of myoblast proliferation and by modulating its expression could promote the early development of skeletal muscle.