Promote Muscle Hypertrophy Research Articles

MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase-β and is regulated by lnc-mg.

Skeletal muscle is an important and complex organ with a variety of functions in humans and animals. Skeletal myogenesis is a multistep and complex process, and increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play critical roles in skeletal myogenesis. In this study the expression of miR-351-5p is dynamically regulated during skeletal myogenesis in vitro and in vivo. Cell-counting kit-8, qRT-PCR, and EdU immunofluorescence analysis showed that miR-351-5p overexpression promoted the proliferation and inhibited the differentiation of C2C12 myoblast, whereas inhibition of miR-351-5p had the opposite effect. In addition, miR-351-5p mediated the regulation of muscle fiber type transition in vivo. In vitro, loss of miR-351-5p in muscle tissues promoted muscle hypertrophy and increased slow-twitch fibers in the gastrocnemius muscles of mice. Luciferase reporter assay and functional analyses demonstrated that lactamase β ( LACTB) is a direct target of miR-351-5p involved in the regulation of skeletal myogenesis. Expression levels of a myogenesis-associated lncRNA ( lnc-mg) correlated negatively with miR-351-5p and positively with LACTB during C2C12 myoblast proliferation and differentiation. Further analyses showed that lnc-mg acted as a molecular sponge for miR-351-5p, demonstrating its involvement in the negative regulation of LACTB by miR-351-5p during skeletal myogenesis. These findings indicate that miRNA-351-5p functions in skeletal myogenesis by targeting LACTB and is regulated by lnc-mg, supporting the role of the competing endogenous RNA network in skeletal myogenesis.-Du, J., Zhang, P., Zhao, X., He, J., Xu, Y., Zou, Q., Luo, J., Shen, L., Gu, H., Tang, Q., Li, M., Jiang, Y., Tang, G., Bai, L., Li, X., Wang, J., Zhang, S., Zhu, L. MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase β and is regulated by lnc-mg.

The DNA methylation status of MyoD and IGF-I genes are correlated with muscle growth during different developmental stages of Japanese flounder (Paralichthys olivaceus).

Many genes related to muscle growth modulate myoblast proliferation and differentiation and promote muscle hypertrophy. MyoD is a myogenic determinant that contributes to myoblast determination, and insulin-like growth factor 1 (IGF-I) interacts with MyoD to regulate muscle hypertrophy and muscle mass. In this study, we aimed to assess DNA methylation and mRNA expression patterns of MyoD and IGF-I during different developmental stages of Japanese flounder, and to examine the relationship between MyoD and IGF-I gene. DNA and RNA were extracted from muscles, and DNA methylation of MyoD and IGF-I promoter and exons was detected by bisulfite sequencing. The relative expression of MyoD and IGF-I was measured by quantitative polymerase chain reaction. IGF-I was measured by radioimmunoassay. Interestingly, the lowest expression of MyoD and IGF-I emerged at larva stage, and the mRNA expression was negatively associated with methylation. We hypothesized that many skeletal muscle were required to complete metamorphosis; thus, the expression levels of MyoD and IGF-I genes increased from larva stage and then decreased. The relative expression levels of MyoD and IGF-I exhibited similar patterns, suggesting that MyoD and IGF-I regulated muscle growth through combined effects. Changes in the concentrations of IGF-I hormone were similar to those of IGF-I gene expression. Our results the mechanism through which MyoD and IGF-I regulate muscle development and demonstrated that MyoD interacted with IGF-I to regulate muscle growth during different developmental stages.

Pharmacology of doping agents—mechanisms promoting muscle hypertrophy

Doping with performance enhancing substances in professional andamateur sports has increasingly gained awareness. Furthermore, not only thenumber but also the variety of substances detected in sports has increased.Intending muscle growth, anabolic androgenic steroids (AAS) have beencomplemented by selective androgen receptor modulators (SARMs), β₂-adrenergicagonists, estrogen receptor (ER) β agonists and peptide-hormones like growthhormone (GH), insulin-like growth factor-1 (IGF-1) and insulin. However, withrespect to therapeutic use, drugs which increase anabolic actions in the bodyare highly desired for treatment of cachexia, sarcopenia, etc.<br />The aim of the following review is to elaborate on the agents’similarities and differences in mechanisms inducing muscle hypertrophy whilegiving an overview of the relevant signalling cascades. In addition to that,potential agents for treatment of catabolic diseases are identified.Information, onwhich this paper is based on, hasbeen collected from various publications which have been published inhigh-quality scientific journals.<br />The insight obtained has shown that signalling pathways mediatinggenomic actions of steroids have already been well-characterised, while thereis still need for further research on the mechanisms of non-genomicactions and downstream pathways as well as on those of SARMs and β₂-adrenergicagonists’ action. A new and promising target is the estrogen receptor β. Theuse of ER-β agonists, which are proposed to activate anabolic mechanismsindependently from androgen receptor activation, may prevent the non-desiredandrogenic effects, which are associated with AAS administration. Thus, theymay be considered a promising alternative for treatment of diseases, whichcause loss of muscle mass and cachexia. In this context, phytoecdysteroids,such as ecdysterone etc, are considered as an interesting class of substances,where further investigations are highly desired. Furthermore, some peptidehormones also promote muscle hypertrophy. The signalling mechanisms of growthhormone, IGF-1 and insulin are summarised. Finally, the potential of myostatininhibition is discussed.

Impact of Resistance Training on Skeletal Muscle Mitochondrial Biogenesis, Content, and Function.

Skeletal muscle metabolic and contractile properties are reliant on muscle mitochondrial and myofibrillar protein turnover. The turnover of these specific protein pools is compromised during disease, aging, and inactivity. Oppositely, exercise can accentuate muscle protein turnover, thereby counteracting decay in muscle function. According to a traditional consensus, endurance exercise is required to drive mitochondrial adaptations, while resistance exercise is required to drive myofibrillar adaptations. However, concurrent practice of traditional endurance exercise and resistance exercise regimens to achieve both types of muscle adaptations is time-consuming, motivationally demanding, and contended to entail practice at intensity levels, that may not comply with clinical settings. It is therefore of principle interest to identify effective, yet feasible, exercise strategies that may positively affect both mitochondrial and myofibrillar protein turnover. Recently, reports indicate that traditional high-load resistance exercise can stimulate muscle mitochondrial biogenesis and mitochondrial respiratory function. Moreover, fatiguing low-load resistance exercise has been shown capable of promoting muscle hypertrophy and expectedly entails greater metabolic stress to potentially enhance mitochondrial adaptations. Consequently, fatiguing low-load resistance exercise regimens may possess the ability to stimulate muscle mitochondrial adaptations without compromising muscle myofibrillar accretion. However, the exact ability of resistance exercise to drive mitochondrial adaptations is debatable, not least due to some methodological challenges. The current review therefore aims to address the evidence on the effects of resistance exercise on skeletal muscle mitochondrial biogenesis, content and function. In prolongation, a perspective is taken on the specific potential of low-load resistance exercise on promoting mitochondrial adaptations.

LncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.

Long noncoding RNAs (lncRNAs) have been reported to play diverse roles in biologic and pathologic processes, including myogenesis. We found that lncRNA AK017368 is highly expressed in skeletal muscle cells. Functional analyses showed that overexpression of AK017368 promoted proliferation and restrained differentiation of myoblasts; whereas inhibition of AK017368 had completely opposite effects in vitro In mice, knockdown of AK017368 promoted muscle hypertrophy in vivo RNA molecules of AK017368 acted mechanistically as competing endogenous RNAs to target micro-RNA (miR)-30c, which was supported by the results of bioinformatics analyses and dual-luciferase reporter assays. It has been shown that lncRNA AK017368 competes with trinucleotide repeat containing-6A (Tnrc6a) for miR-30c. Tnrc6a was previously reported to promote proliferation and inhibit differentiation of myoblast cells, whereas miR-30c targets the 3'-UTR of Tnrc6a mRNA to weaken its function. Taken together, lncRNA AK017368 promotes proliferation and inhibits differentiation of myoblast cells by attenuating function of miR-30c.-Liang, T., Zhou, B., Shi, L., Wang, H., Chu, Q., Xu, F., Li, Y., Chen, R., Shen, C., Schinckel, A. P. lncRNA AK017368 promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c.

Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis.

Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. We showed that MAGIC-F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors.

Metformin to Augment Strength Training Effective Response in Seniors (MASTERS): study protocol for a randomized controlled trial

BackgroundMuscle mass and strength are strong determinants of a person’s quality of life and functional independence with advancing age. While resistance training is the most effective intervention to combat age-associated muscle atrophy (sarcopenia), the ability of older adults to increase muscle mass and strength in response to training is blunted and highly variable. Thus, finding novel ways to complement resistance training to improve muscle response and ultimately quality of life among older individuals is critical. The purpose of this study is to determine whether a commonly prescribed medication called metformin can be repurposed to improve the response to resistance exercise training by altering the muscle tissue inflammatory environment.Methods/designIndividuals aged 65 and older are participating in a two-site, randomized, double-blind, placebo-controlled trial testing the effects of metformin or placebo on muscle size, strength, and physical function when combined with a progressive resistance training program. Participants consume 1700 mg of metformin per day or placebo for 2 weeks before engaging in a 14-week progressive resistance training regimen, with continued metformin or placebo. Participants are then monitored post-training to determine if the group taking metformin derived greater overall benefit from training in terms of muscle mass and strength gains than those on placebo. Muscle biopsies are taken from the vastus lateralis at three time points to assess individual cellular and molecular adaptations to resistance training and also changes in response to metformin.DiscussionThe response of aged muscles to a resistance training program does not always result in a positive outcome; some individuals even experience a loss in muscle mass following resistance training. Thus, adjuvant therapies, including pharmacological ones, are required to optimize response to training in those who do not respond and may be at increased risk of frailty. This is the first known metformin repurposing trial in non-diseased individuals, aimed specifically at the resistance exercise “non-responder” phenotype present in the aging population. The overall goal of this trial is to determine if combined exercise-metformin intervention therapy will benefit older individuals by promoting muscle hypertrophy and strength gains, thereby maintaining functional independence.Trial registrationClinicalTrials.gov, NCT02308228. Registered on 25 November 2014.

Lnc-mg is a long non-coding RNA that promotes myogenesis

Recent studies indicate important roles for long noncoding RNAs (lncRNAs) as essential regulators of myogenesis and adult skeletal muscle regeneration. However, the specific roles of lncRNAs in myogenic differentiation of adult skeletal muscle stem cells and myogenesis are still largely unknown. Here we identify a lncRNA that is specifically enriched in skeletal muscle (myogenesis-associated lncRNA, in short, lnc-mg). In mice, conditional knockout of lnc-mg in skeletal muscle results in muscle atrophy and the loss of muscular endurance during exercise. Alternatively, skeletal muscle-specific overexpression of lnc-mg promotes muscle hypertrophy. In vitro analysis of primary skeletal muscle cells shows that lnc-mg increases gradually during myogenic differentiation and its overexpression improves cell differentiation. Mechanistically, lnc-mg promotes myogenesis, by functioning as a competing endogenous RNA (ceRNA) for microRNA-125b to control protein abundance of insulin-like growth factor 2. These findings identify lnc-mg as a novel noncoding regulator for muscle cell differentiation and skeletal muscle development.

Systematic review of the synergist muscle ablation model for compensatory hypertrophy.

The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy

BackgroundKorean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle.MethodsWe examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model.ResultsInterestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice.ConclusionsOur results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

Effects of immunocastration and β-adrenergic agonists on the performance and carcass traits of feedlot finished Nellore cattle

β-Adrenergic agonists (β-AA) are non-hormonal growth promoters which promote muscle hypertrophy in supplemented animals. The effects of two β-AA in combination with the immunocastration technique on the performance and carcass traits were evaluated using 96 feedlot Nellore males in a randomized complete block design with two sex conditions (immunocastrated (IC) v. non-castrated (NC)) and three treatments: CON (no β-agonists added), RH (300 mg of ractopamine hydrochloride/day, for 33 days) or ZH (80 mg of zilpaterol·hydrochloride animal/day for 30 days, removed 3 days for required withdrawal period). The trial was carried for 100 days where in the first 70 days animals did not receive β-AA (phase 1) and during the last 30 days they were treated with β-AA (phase 2). The performance and ultrasound measurements of longissimus muscle area (LMA), backfat thickness (BFT) and rump fat thickness (RFT) were evaluated in both phases. No sex condition v. treatment interactions were observed for any trait. The NC animals had higher average daily gain (ADG) and final BW than the IC animals, but they did not differ in dry matter intake (DMI) and feed efficiency (gain to feed). The NC animals showed greater LMA (P=0.0001) and hot carcass weight (P=0.0006), and smaller BFT (P=0.0007), RFT (P=0.0039) and percentage of kidney, pelvic and heart fat (P<0.0001) when compared with IC animals. The animals fed ZH showed greater ADG (P=0.0002), G : F (P<0.0001) and dressing per cent (P=0.0136) than those fed RH and CON diets. No differences in BW and DMI were observed. A interaction between treatment and time on feed was observed for LMA and BFT, in which the animals fed ZH diet showed greater LMA (P<0.01) and lower BFT (P<0.01) at 100 days than the animals fed RH and CON diets, whereas RH and CON diets did not differ. Immunocastration decreases muscle development and increases carcass finishing. In contrast, β-AA increases muscle and decreases fat deposition. The ZH has a higher action on the muscle metabolism than animals fed RH diet. However, RH diet achieves a better balance because it has an intermediary performance between non-supplemented and ZH animals and does not decrease the carcass fat.

Analysis of concentric and eccentric contractions in biceps brachii muscles using surface electromyography signals and multifractal analysis.

Muscle contractions can be categorized into isometric, isotonic (concentric and eccentric) and isokinetic contractions. The eccentric contractions are very effective for promoting muscle hypertrophy and produce larger forces when compared to the concentric or isometric contractions. Surface electromyography signals are widely used for analyzing muscle activities. These signals are nonstationary, nonlinear and exhibit self-similar multifractal behavior. The research on surface electromyography signals using multifractal analysis is not well established for concentric and eccentric contractions. In this study, an attempt has been made to analyze the concentric and eccentric contractions associated with biceps brachii muscles using surface electromyography signals and multifractal detrended moving average algorithm. Surface electromyography signals were recorded from 20 healthy individuals while performing a single curl exercise. The preprocessed signals were divided into concentric and eccentric cycles and in turn divided into phases based on range of motion: lower (0°-90°) and upper (>90°). The segments of surface electromyography signal were subjected to multifractal detrended moving average algorithm, and multifractal features such as strength of multifractality, peak exponent value, maximum exponent and exponent index were extracted in addition to conventional linear features such as root mean square and median frequency. The results show that surface electromyography signals exhibit multifractal behavior in both concentric and eccentric cycles. The mean strength of multifractality increased by 15% in eccentric contraction compared to concentric contraction. The lowest and highest exponent index values are observed in the upper concentric and lower eccentric contractions, respectively. The multifractal features are observed to be helpful in differentiating surface electromyography signals along the range of motion as compared to root mean square and median frequency. It appears that these multifractal features extracted from the concentric and eccentric contractions can be useful in the assessment of surface electromyography signals in sports medicine and training and also in rehabilitation programs.

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass.

The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network-responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles.

Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy.

Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting.

Digestive enzymes reduce quality differences between plant and animal proteins: a double-blind crossover study

Background Whey protein is considered to be the optimal protein source to support muscle protein synthesis (MPS) with resistance training, based on its amino acid content (high in leucine), rapid digestibility, and high bioavailability within the muscle tissue [1]. Athletes can choose from different plant protein sources (e.g. soy, rice, pea, hemp), which differ in numerous ways, such as the presence of allergens (milk, soy), cholesterol, saturated fats, digestion rate (fast, intermediate, or slow absorption of amino acids), or the relative amount of individual amino acids. Rice protein has been shown to promote muscle hypertrophy with resistance training comparable to whey protein [2]. 48g of rice or whey protein isolate immediately post-exercise during an 8-week progressive, non-linear resistance-training protocol increased lean body mass, muscle thickness, and strength with no differences between groups. The findings are likely due to the high dose of protein used in the study, providing amounts of leucine greater than the 1.7 to 3.5g that has been proposed to be the range for optimal MPS. Rice protein, compared to whey (fast) and casein (slow), is an intermediate digesting protein and shows a 6.8% lower total amino acid appearance in the blood [3]. While dairy protein sources contain simple sugars, mainly lactose, plant proteins contain more complex carbohydrates, including fibers and glycoproteins. This study sought to investigate if co-ingestion of a plant protein specific digestive enzyme blend (Digest-All VP, a proprietary enzyme blend consisting of protease 6.0, protease 4.5, peptidase, bromelain and alpha-galactosidase, Chemi-Source, Inc., Oceanside, CA) can reduce the significant differences in amino acid appearance in the blood between plant and animal proteins.

Myostatin dysfunction impairs force generation in extensor digitorum longus muscle and increases exercise-induced protein efflux from extensor digitorum longus and soleus muscles.

Myostatin dysfunction promotes muscle hypertrophy, which can complicate assessment of muscle properties. We examined force generating capacity and creatine kinase (CK) efflux from skeletal muscles of young mice before they reach adult body and muscle size. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of Berlin high (BEH) mice with dysfunctional myostatin, i.e., homozygous for inactivating myostatin mutation, and with a wild-type myostatin (BEH+/+) were studied. The muscles of BEH mice showed faster (P < 0.01) twitch and tetanus contraction times compared with BEH+/+ mice, but only EDL displayed lower (P < 0.05) specific force. SOL and EDL of age-matched but not younger BEH mice showed greater exercise-induced CK efflux compared with BEH+/+ mice. In summary, myostatin dysfunction leads to impairment in muscle force generating capacity in EDL and increases susceptibility of SOL and EDL to protein loss after exercise.

Load-controlled moderate and high-intensity resistance training programs provoke similar strength gains in young women.

While current exercise guidelines recommend progressive, high-intensity resistance training (RT) to promote muscle hypertrophy and strength gains, controversy exists regarding the efficacy of lighter-load RT. We compared 2 work-matched RT interventions that differed in training intensity. Fifteen women underwent 10 weeks of unilateral knee extensor RT. One leg was trained at increasing intensity (intensity leg, InL, 50-80% 1-repetition maximum [1-RM]), and training progression in the contralateral leg (volume leg, VoL, 50% 1-RM) was based on increasing training volumes. Quadriceps muscle size (ultrasound, dual energy X-ray absorptiometry) and strength (isokinetic dynamometry) were assessed on 4 occasions. Both training programs induced significant, yet comparable increases in muscle size (InL: +4.6-12%, VoL: +3.1-11%) and strength (InL: +10-16%, VoL: +10-14%). Training at lower than commonly suggested intensities may be an equally effective alternative form of RT. Factors other than training intensity, such as the total mechanical work during training, may strongly affect the training response.

The effects of protein supplements on muscle mass, strength, and aerobic and anaerobic power in healthy adults: a systematic review.

Protein supplements are frequently consumed by athletes and recreationally active adults to achieve greater gains in muscle mass and strength and improve physical performance. This review provides a systematic and comprehensive analysis of the literature that tested the hypothesis that protein supplements accelerate gains in muscle mass and strength resulting in improvements in aerobic and anaerobic power. Evidence statements were created based on an accepted strength of recommendation taxonomy. English language articles were searched through PubMed and Google Scholar using protein and supplements together with performance, exercise, strength, and muscle, alone or in combination as keywords. Additional articles were retrieved from reference lists found in these papers. Studies recruiting healthy adults between 18 and 50 years of age that evaluated the effects of protein supplements alone or in combination with carbohydrate on a performance metric (e.g., one repetition maximum or isometric or isokinetic muscle strength), metrics of body composition, or measures of aerobic or anaerobic power were included in this review. The literature search identified 32 articles which incorporated test metrics that dealt exclusively with changes in muscle mass and strength, 5 articles that implemented combined resistance and aerobic training or followed participants during their normal sport training programs, and 1 article that evaluated changes in muscle oxidative enzymes and maximal aerobic power. All papers were read in detail, and examined for experimental design confounders such as dietary monitoring, history of physical training (i.e., trained and untrained), and the number of participants studied. Studies were also evaluated based on the intensity, frequency, and duration of training, the type and timing of protein supplementation, and the sensitivity of the test metrics. For untrained individuals, consuming supplemental protein likely has no impact on lean mass and muscle strength during the initial weeks of resistance training. However, as the duration, frequency, and volume of resistance training increase, protein supplementation may promote muscle hypertrophy and enhance gains in muscle strength in both untrained and trained individuals. Evidence also suggests that protein supplementation may accelerate gains in both aerobic and anaerobic power. To demonstrate measureable gains in strength and performance with exercise training and protein supplementation, many of the studies reviewed recruited untrained participants. Since skeletal muscle responses to exercise and protein supplementation differ between trained and untrained individuals, findings are not easily generalized for all consumers who may be considering the use of protein supplements. This review suggests that protein supplementation may enhance muscle mass and performance when the training stimulus is adequate (e.g., frequency, volume, duration), and dietary intake is consistent with recommendations for physically active individuals.

G protein coupled receptor 56 is a target gene of the PGC‐1α4 isoform and regulates overload‐induced muscle hypertrophy (1163.15)

The PGC‐1α isoform referred to as PGC‐1α4 has recently been shown to promote muscle hypertrophy and attenuate muscle wasting. Although it has been shown that PGC‐1α4 can regulate the expression of IGF‐1 and myostatin, two potent regulators of muscle mass, its detailed mechanism of action remains unclear. Gene array analysis has identified the G‐protein coupled receptor 56 to be a transcriptional target of PGC‐1α4. GPR56 is a newly defined adhesion receptor which can mediate both G protein coupled signalling and integrin function, although little in know about its function in skeletal muscle. We have found the anabolic effect of PGC‐1α4 is, in part dependent on GPR56 signalling as knockdown of GPR56 attenuates PGC‐1α4‐induced muscle hypertrophy in vitro. Forced expression of GPR56 in primary myotubes results in mild hypertrophy. However, when forced expression of GPR56 is accompanied by the addition of its ligand, Collagen III, it drives robust myotube hypertrophy. In vivo models of overload‐induced muscle hypertrophy increase GPR56 expression while GPR56 loss of funtion attenuates the hypertrophic response to mechanical overload. Lastly, we show muscle GPR56 expression is increased during human resistance exercise. In conclusion, we have discovered GPR56 is a PGC‐1α4 transcriptional target and could play a role in muscle hypertrophy induced by resistance/loading‐type exercise.

Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.