Stimulate Muscle Growth Research Articles

Irisin promotes tilapia muscle cell growth and amino acid uptake via IGF-1 signaling.

Irisin is a recently discovered myokine that facilitates the browning of white adipose tissue, increases glucose uptake in skeletal muscle, and influences metabolic processes in the liver. However, its potential effects on amino acid absorption remained largely unexplored. This study aimed to elucidate the role of irisin in modulating amino acid uptake and delineate the underlying molecular mechanisms involved. To this end, juvenile tilapia were administered intraperitoneal irisin injections at 100 ng/g body weight over 8 weeks. Evaluation of various physiological parameters revealed that irisin supplementation significantly improved the specific growth rate and feed conversion efficiency while reducing feed consumption. Muscle tissue analysis revealed that irisin significantly modified the proximate composition by increasing protein content and reducing lipid levels. It also significantly raised the levels of both essential and non-essential amino acids in the muscle. Histological analysis demonstrated that irisin-stimulated muscle growth through hyperplasia rather than hypertrophy, corroborated by upregulated IGF-1 mRNA and downregulated myostatin mRNA expression. Mechanistic studies in cultured tilapia muscle cells elucidated that irisin activated integrin receptors on muscle cells, which subsequently engaged IGF-1/IGF-1R signaling. Downstream of IGF-1R activation, irisin simultaneously stimulates the ERK1/2 and PI3K/mTORC2/Akt pathways. The convergence of these pathways upregulates L-type amino acid transporter 1 expression, thereby augmenting amino acid uptake into muscle cells. In summary, irisin supplementation in tilapia leads to improved muscle growth, predominantly via hyperplasia and augmented amino acid assimilation, governed by intricate cellular signaling pathways. These findings provide valuable aquaculture applications and novel insights into muscle development.

Regeneration of Neuromuscular Synapses by Inhibition of the Prostaglandin Degrading Enzyme 15-PGDH

Background: Skeletal muscles require voluntary activation to move, which is supplied via motor neurons. The terminal axons of motor neurons innervate muscle fibers at the neuromuscular junction (NMJ). NMJ degeneration increases with age and injury, decreasing muscle contractility and strength and severely reducing individuals’ quality of life. Treatments able to restore NMJ integrity and muscle innervation after injury and in aging are currently lacking. Aim: Our lab has recently shown that boosting prostaglandin E2 (PGE2) levels in aged mice by inhibiting its degrading enzyme 15-prostaglandin dehydrogenase (15-PGDH) stimulates muscle growth and restores muscle strength and endurance. The present study aimed at investigating whether 15-PGDH inhibition promotes muscle reinnervation and NMJ restoration, thus improving muscle function. Methods and results: We treated young (3-month) and old (27-month) mice with a small molecule compound with high specificity for 15-PGDH inhibition for 30 days. Old treated mice displayed increased muscle mass and strength (p<0.05) compared to aged control mice. While aged control displayed, as expected, a high percentage of denervated NMJ (21.6%), denervation was partially rescued by 15-PGDH inhibition (12.1%, p<0.05). Similarly, NMJ fragmentation was lower in treated versus control mice (18.1% vs 29.3%, p<0.05). To translate our findings to a more acute scenario, we induced nerve-crush injury in young mice (3-month) and treated animals with 15-PGDH inhibition during injury recovery. Treated mice were able to exert a 37.2% higher tetanic force 14 days after injury compared to control mice. This was accompanied by increased muscle mass and specific force (+32.2%, p<0.05) and an increased percentage of innervated NMJs (97.4% versus 84.5%) in treated versus control mice, suggesting that 15-PGDH inhibition was promoting NMJ restoration and muscle reinnervation after injury. Conclusion: In this study we identify 15-PGDH inhibition as a new potential therapeutic strategy to promote reinnervation of NMJs and strength recovery after acute or chronic denervation due to injury or aging. Funding: E.M. is supported by a “Wu Tsai Human Performance Alliance” fellowship. This study was supported by the Donald E. and Delia B. Baxter Foundation, the Li Ka Shing Foundation, Milky Way Research Foundation MWRF-216064, California Institute for Regenerative Medicine grant DISC2-10604, and U.S. National Institutes of Health (NIH) grants R01-AG020961, R01-AG069858, and R01-RHG009674 to H.M.B. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

From gains to gaps? How Selective Androgen Receptor Modulator (SARM) YK11 impact hippocampal function: In silico, in vivo, and ex vivo perspectives

Selective Androgen Receptor Modulators (SARMs), particularly (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic-acid-methyl-ester (YK11), are increasingly popular among athletes seeking enhanced performance. Serving as an Androgen Receptor (AR) agonist, YK11 stimulates muscle growth while inhibiting myostatin. Our study delved into the impact of YK11 on the rat hippocampus, analyzing potential alterations in neurochemical mechanisms and investigating its synergistic effects with exercise (EXE), based on the strong relationship between SARM users and regular exercise. Utilizing Physiologically Based Pharmacokinetic (PBPK) modeling, we demonstrated YK11 remarkable brain permeability, with molecular docking analysis revealing YK11 inhibitory effects on 5-alpha-reductase type II (5αR2), suggesting high cell bioavailability. Throughout a 5-week experiment, we divided the animals into the following groups: Control, YK11 (0.35 g/kg), EXE (swimming exercise), and EXE + YK11. Our findings showed that YK11 displayed a high binding affinity with AR in the hippocampus, influencing neurochemical function and modulating aversive memory consolidation, including the downregulation of the BDNF/TrkB/CREB signaling, irrespective of EXE combination. In the hippocampus, YK11 increased pro-inflammatory IL-1β and IL-6 cytokines, while reducing anti-inflammatory IL-10 levels. However, the EXE + YK11 group counteracted IL-6 effects and elevated IL-10. Analysis of apoptotic proteins revealed heightened p38 MAPK activity in response to YK11-induced inflammation, initiating the apoptotic cascade involving Bax/Bcl-2/cleaved caspase-3. Notably, the EXE + YK11 group mitigated alterations in Bcl-2 and cleaved caspase-3 proteins. In conclusion, our findings suggest that YK11, at anabolic doses, significantly alters hippocampal neurochemistry, leading to impairments in memory consolidation. This underscore concerns about the misuse risks of SARMs among athletes and challenges common perceptions of their minimal side effects.

The Effectiveness of Blood Flow Restriction Technique Combined with Low-Resistance Exercise in the Postoperative Rehabilitation of Patients Following Knee Surgery: A Narrative Review and Update of Evidence-Based Physiotherapy Practice

<b>Background:</b> Blood flow restriction (BFR) therapy has emerged as a promising rehabilitation approach after knee surgery. The technique involves the use of a tourniquet or cuff to limit blood flow to the affected limb during low-resistance exercise, which creates a hypoxic environment thought to stimulate muscle growth and improve muscle function. <b>Objective:</b> Our scoping review aims to examine the current literature on the effectiveness of BFR combined with low-resistance exercise on rehabilitation after knee surgery. <b>Method: </b>The Google Scholar, PubMed, and PEDro databases were searched using relevant key-words. Studies that met the inclusion criteria were selected for analysis. The data from the selected studies were analyzed, categorized, and summarized to provide an overview of the findings. <b>Results:</b> In total, 12 studies met the inclusion criteria and were included in the review. Outcomes such as pain, strength, and range of motion were assessed. <b>Conclusion: </b>The results suggest that BFR and low-resistance exercise can be effective in improving patient outcomes following knee surgery. However, the heterogeneity of the studies made it difficult to determine the most effective approach. Further research is needed to identify the optimal dosage, frequency, and duration of BFR and low-resistance exercise for knee surgery rehabilitation.

Effect weight training on muscular hypertrophy: a systematic review

Background and Study Aim. In the context of the growing importance of strength training, the analysis of the impact of strength loads on muscle hypertrophy becomes increasingly significant. Therefore, it is critical to comprehend both the effects of strength training on stimulating muscle growth and the potential ramifications. This study aimed to systematically analyze and collate the existing scientific evidence on the effects of weight training on muscle hypertrophy. Material and Methods. The research method involved the source selection of relevant studies from various databases, with predefined inclusion criteria. A thorough literature search was conducted, followed by data extraction focusing on study design, subject population, type of weight training, duration, and outcome measures of muscle hypertrophy. Databases such as PubMed, Google Scholar and Scopus were the primary sources of literature searches. Results. The results of this systematic review indicated evidence supporting the positive effect of weight training on muscle hypertrophy in most of the studies included. However, some studies produced controversial findings or even showed no significant impact. Factors such as variations in exercise type, intensity, and frequency also influence the outcome of weight training on muscle growth. Conclusions. While weight training has the potential to stimulate muscle hypertrophy, its effects may vary based on various factors. Therefore, selecting the correct type of exercise, setting the appropriate intensity, and planning the frequency of activity is essential in achieving optimal results. This study has strong relevance in fostering effective and safe exercise programs.It can also serve as a basis for further research in exploring other factors that may influence weight training-induced muscle hypertrophy outcomes.

Optimizing competitive period training for qualified bodybuilders: an analysis of muscle mass development and physique enhancement

This article presents an analysis of the preparation of qualified bodybuilders during the competitive period. The study focuses on the impact of training and nutrition on the development of muscle mass and achieving an optimal physique for bodybuilding competitions.
 During the competitive mesocycle, bodybuilders utilized a structured training regimen that consisted of four microcycles: the adaptation microcycle, impact microcycle, recovery microcycle, and competitive microcycle. Each microcycle targeted specific muscle groups and employed varying intensities and volumes of training to stimulate muscle growth and preserve mass.
 The research involved 15 qualified bodybuilders affiliated with the regional bodybuilding federations of Kharkiv and Poltava. The study duration spanned 28 days, and the participants' muscle group circumferences were measured at the beginning and end of the research period. Significant statistical differences were observed in the circumference measurements of the shoulder, waist, and thigh (p<0.05). Shoulder circumference increased from 44.1±0.8 cm to 46.2±0.5 cm, waist circumference decreased from 84.2±2.3 cm to 77.3±1.8 cm, and thigh circumference increased from 62.3±0.9 cm to 64.8±0.6 cm.
 The results revealed a positive progression in muscle groups, indicating the effectiveness of the competitive mesocycle in bodybuilding competitions. The proposed structured training regimen and microcycle content can be recommended for practical implementation in the training process of qualified bodybuilders. This may further enhance their ability to achieve optimal physique and excel in competitions.
 Future research prospects involve the development of a structured training regimen and content for the transitional period of bodybuilding preparation. This can lead to even more effective preparation and performance improvements during competitive events.
 In conclusion, the study highlights the importance of a well-designed training regimen and proper nutrition for qualified bodybuilders during the competitive period. The findings provide valuable insights for athletes, coaches, and sports scientists to optimize training strategies and foster success in bodybuilding competitions.

Morphological Medial Gastrocnemius Muscle Growth in Ambulant Children with Spastic Cerebral Palsy: A Prospective Longitudinal Study

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of gross motor functional limitations on altered muscle growth remains unclear. This prospective longitudinal study modelled morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III = 47/22/18). Ultrasound assessments were performed during 2-year follow-up and repeated for a minimal interval of 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I and GMFCS-II&III. MV and CSA growth trajectories showed a piecewise model with two breakpoints, with the highest growth before 2 years and negative growth rates after 6-9 years. Before 2 years, children with GMFCS-II&III already showed lower growth rates compared to GMFCS-I. From 2 to 9 years, the growth rates did not differ between GMFCS levels. After 9 years, a more pronounced reduction in normalized CSA was observed in GMFCS-II&III. Different trajectories in ML growth were shown between the GMFCS level subgroups. These longitudinal trajectories highlight monitoring of SCP muscle pathology from early ages and related to motor mobility. Treatment planning and goals should stimulate muscle growth.

Generation of myostatin gene-edited blotched snakehead (Channa maculata) using CRISPR/Cas9 system

Blotched snakehead (Channa maculata) is one of the most important freshwater fish in China. Genome editing is of great potential in generating new snakehead strains with valuable economic traits without integration of exogenous genes. Myostatin (Mstn) inhibits the development and growth of skeletal muscle in vertebrates, including teleosts. Mstn mutations induced by genome editing can stimulate muscle growth and development, therefore Mstn is an appropriate candidate to breed the fast-growing snakehead strain. For this study, one orthologous Mstn gene was characterized in C. maculata, designated as CmMstn, which possessed the relatively conserved gene and protein structure. CmMstn had the highest expression level and sexual dimorphism in muscles. Two CRISPR/Cas9 target sites were designed to generate knockout mutants within the mature mRNA sequence of CmMstn located in Exon I and Exon II. 1 nL mixture solution of 200 pg gRNA and 300 pg Cas9 protein was directly microinjected into each snakehead embryonic yolk at 1⁓4 cell stage. Mstn was efficiently edited by CRISPR/Cas9 system in shakehead, and all designed gRNAs effectively worked at their target sites with high mutagenesis efficiencies, from 40.0% to 53.3%. The majority of mutations were frame-shift and resulted in premature termination of transcription and disruption of the molecular function of CmMstn protein. Furthermore, we obtained four founders (F0) of snakehead with the mutated Mstn gene in their primordial germ cells, and nineteen F1 offspring of the F0 mutants mated with wild-type individuals were displayed to carry Mstn null alleles. It is the first application of genome editing technology in blotched snakehead, and CRISPR/Cas9 system successfully edit the primordial germ cells. Our findings will accelerate our understanding of the role of Mstn gene in snakehead growth, and speed up the cultivation of the fast-growing snakehead strain.

The Effect of Blood Flow Restriction Therapy on Shoulder Function Following Shoulder Stabilization Surgery: A Case Series.

Traumatic shoulder instability is a common injury in athletes and military personnel. Surgical stabilization reduces recurrence, but athletes often return to sport before recovering upper extremity rotational strength and sport-specific abilities. Blood flow restriction (BFR) may stimulate muscle growth without the need for heavy resistance training post-surgically. To observe changes in shoulder strength, self-reported function, upper extremity performance, and range of motion (ROM) in military cadets recovering from shoulder stabilization surgery who completed a standard rehabilitation program with six weeks of BFR training. Prospective case series. Military cadets who underwent shoulder stabilization surgery completed six weeks of upper extremity BFR training, beginning post-op week six. Primary outcomes were shoulder isometric strength and patient-reported function assessed at 6-weeks, 12-weeks, and 6-months postoperatively. Secondary outcomes included shoulder ROM assessed at each timepoint and the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST), the Upper Extremity Y-Balance Test (UQYBT), and the Unilateral Seated Shotput Test (USPT) assessed at the six-month follow-up. Twenty cadets performed an average 10.9 BFR training sessions over six weeks. Statistically significant and clinically meaningful increases in surgical extremity external rotation strength (p < 0.001; mean difference, .049; 95% CI: .021, .077), abduction strength (p < 0.001; mean difference, .079; 95% CI: .050, .108), and internal rotation strength (p < 0.001; mean difference, .060; CI: .028, .093) occurred from six to 12 weeks postoperatively. Statistically significant and clinically meaningful improvements were reported on the Single Assessment Numeric Evaluation (p < 0.001; mean difference, 17.7; CI: 9.4, 25.9) and Shoulder Pain and Disability Index (p < 0.001; mean difference, -31.1; CI: -44.2, -18.0) from six to 12 weeks postoperatively. Additionally, over 70 percent of participants met reference values on two to three performance tests at 6-months. While the degree of improvement attributable to the addition of BFR is unknown, the clinically meaningful improvements in shoulder strength, self-reported function, and upper extremity performance warrant further exploration of BFR during upper extremity rehabilitation. 4, Case Series.

Creatine: A valuable supplement in aquafeeds?

AbstractCreatine is an amino acid derivate commonly found in vertebrate muscle tissue. Creatine facilitates the recycling of adenosine triphosphate and thus contributes to the energy supply of the muscles as well as the brain. Creatine is used as a supplement for several reasons and its effects in humans, particularly in sports medicine, have been studied excessively. Also, creatine supplementation has been studied for its functions and benefits in terrestrial farm animals. Up to date, little is known about the use of creatine as a supplement in fish nutrition. Yet, due to its many physiological functions, creatine may serve as a valuable supplement in aquafeeds of farmed aquaculture species. Indeed, creatine plays a pivotal role in the fish's muscle and may help to enhance performance of fish reared in aquaculture systems. With regard to swimming exercise, creatine may even amplify its metabolic effects. Upon supplementation, creatine stimulates muscle growth increasing body mass and it has the potential to improve feed utilisation particularly of plant‐based diets. Also, creatine plays a part in osmoregulation when fish adapt to changes in salinity. Furthermore, it may improve product quality upon slaughter. Here, we compile what is known about the many functions of creatine as well as its physiological effects in fish in comparison to mammals. We also highlight its potential beneficial effects as a supplement in aquaculture and infer why creatine can help increase the sustainability of fish feeds.

Effects of Vitamin D Supplementation on Overload‐Induced Muscle Growth and Function in Mice

Muscle hypertrophy induced by functional overload (FO) provides an in vivo model to study muscle growth. Research suggests vitamin D supplementation may stimulate muscle growth and may be associated with increased growth factor levels, such as insulin‐like growth factor‐1 (IGF‐1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). However, it is unclear if vitamin D impacts both muscle hypertrophy and contractile function. We hypothesized that vitamin D supplementation would positively impact the muscle response to a growth stimulus as evidenced by greater hypertrophy, increased IGF‐1, FGF, and VEGF levels, and improved contractile function compared to placebo. Adult mice underwent functional overload (FO) of the plantaris or sham surgery. In vivo plantaris force and fatigue resistance (% of maximal force after 10 contractions) were measured 14d post‐FO or sham in mice receiving daily vitamin D or placebo (n= 8‐10/group). IGF‐1, FGF, and VEGF were measured in the plantaris by ELISA. FO increased plantaris mass, independent of treatment (placebo: 22.8±1.7 vs. 13.4±1.3 and vitamin D: 20.3±3.3 vs. 13.2±0.7 mg, for FO and sham, respectively, p&lt;0.05). Maximal force relative to body mass was unchanged with FO or vitamin D. Significant main effects of FO and vitamin D were found when maximal force was normalized to plantaris mass. With placebo, FO was associated with a significant decrease in force normalized to plantaris mass while vitamin D attenuated this decrease (placebo: 401±48 vs. 871±157 and vitamin D: 679±125 vs. 1062±120 g/g muscle, for FO and sham, respectively, p&lt;0.05). Fatigue resistance was increased with FO, independent of treatment (placebo: 54±3% vs. 40±4% and vitamin D: 63±5% vs. 33±6%, for FO and sham, respectively, p&lt;0.05). IGF‐1 levels were increased in the overloaded plantaris, independent of treatment (placebo: 842±284 vs. 99±9 and vitamin D: 576±138 vs. 115±10 mg/mg, for FO and sham, respectively, p&lt;0.05), but were unchanged in the unloaded tibialis anterior. FGF levels were increased in the overloaded plantaris, independent of treatment (placebo: 378±56 vs. 105±37 and vitamin D: 414±58 vs. 153±82 mg/mg, for FO and sham, respectively, p&lt;0.05). VEGF levels were unchanged with FO and/or Vitamin D. Vitamin D treatment in combination with FO did not significantly improve the ability of skeletal muscle to hypertrophy or increase growth factor expression in response to a growth stimulus. However, vitamin D supplementation may positively impact muscle strength during periods of growth.

Changes in Histological Structure, Interleukin 12, Smooth Muscle Actin and Nitric Oxide Synthase 1. and 3. Expression in the Liver of Running and Non-Running Wistar Rats Supplemented with Bee Pollen or Whey Protein.

Introduction: Bee pollen is a natural substance obtained from flowers by bees. It is a rich source of protein, vitamins and minerals. It can be used as a dietary supplement. Bee pollen has been investigated for the treatment of some diseases with promising potential. It can be helpful in supportive therapy for dyslipidemia, metabolic syndrome, diabetes type 2, as well the prevention and control of coronary heart disease and myocardial infarction. Whey protein is a rich source of amino acids. It is a basic dietary supplement for many athletes, both professional and amateur. It stimulates muscle growth and provides nutrition for cachectic patients. Aim of the study: The objective of the study was to assess the impact of dietary supplementation of bee pollen or whey protein on the Wistar rat liver histological structure and expression of interleukin 12, smooth muscle actin and nitric oxide synthases among running and non-running rats. Material and methods: Thirty male Wistar rats were divided into six equal groups, three running and three non-running. Among both there was one control, one supplemented with bee pollen and one receiving whey proteins. After 8 weeks, all animals were decapitated and their livers were collected. Five micrometer thick slides were prepared and used for classical histological staining and immuno-histochemistry. ImageJ image analysis software was used to measure optical density and immunohistochemistry profile coverage. Results: Among all groups, morphology of liver was similar. In the running control group, expression of interleukin-12 (IL-12) was decreased as well as expression of endothelial nitric oxide synthase (eNOS) in a group of bee pollen supplemented rats. No significant changes in α- smooth muscle actin (α-SMA) expression was observed. Conclusions: Bee pollen is proving to be a questionable choice for athletes as an alternative to whey protein. Bee pollen supplementation affects hepatocyte cellular activity and has hepatoprotective effects. Whey protein performs worse in this regard. Lower antioxidant properties were found in groups supplemented with bee pollen than with whey protein.

Influence of blood flow restriction training on the aerobic capacity: a systematic review and meta-analysis

Background: Blood flow restriction training (also known as KAATSU training) uses professional equipment to apply pressure to the base of the limbs to limit the blood flow at the distal end of the limbs during exercise, thereby stimulating muscle growth and improving muscle strength with a low exercise intensity. This study aimed to conduct a meta-analysis on the effects of blood flow restriction training on aerobic capacity. Methods: A systematic review and quantitative evidence synthesis (QES) was used to examine the effects of blood flow restriction training on the aerobic capacity. A literature search was performed on relevant databases. Search engines used were MEDLINE, EMBASE, PubMed, Web of Science, SPORT-Discus, CINHAL, ScienceDirect, and the Cochrane Library. Search terms were KAATSU training, blood flow restriction training, and occlusion training. Thirteen articles (a total sample size of 246 participants) fulfilled the inclusion criteria and were included. Results: Blood flow restriction training promoted the improvement in aerobic capacity (standard mean difference (SMD) = 0.40, 95% confidence interval (CI) (0.14–0.66), I2 = 0%, p &lt; 0.01), showing no publication bias. In subgroup analysis, intervention methods, and intervention frequencies had different effects on aerobic capacity. Conclusions: Blood flow restriction training, which is a low intensity exercise, significantly affected aerobic capacity. Twelve blood flow restriction training sessions a week achieved significantly better results than a frequency of two to four training sessions per week. A daily blood flow restriction training session of 6 to 30 min significantly improved aerobic capacity.

Activation of Akt-mTORC1 signalling reverts cancer-dependent muscle wasting.

BackgroundCancer‐related muscle wasting occurs in most cancer patients. An important regulator of adult muscle mass and function is the Akt–mTORC1 pathway. While Akt–mTORC1 signalling is important for adult muscle homeostasis, it is also a major target of numerous cancer treatments. Which role Akt–mTORC1 signalling plays during cancer cachexia in muscle is currently not known. Here, we aimed to determine how activation or inactivation of the pathway affects skeletal muscle during cancer cachexia.MethodsWe used inducible, muscle‐specific Raptor ko (mTORC1) mice to determine the effect of reduced mTOR signalling during cancer cachexia. On the contrary, in order to understand if skeletal muscles maintain their anabolic capacity and if activation of Akt–mTORC1 signalling can reverse cancer cachexia, we generated mice in which we can inducibly activate Akt specifically in skeletal muscles.ResultsWe found that mTORC1 signalling is impaired during cancer cachexia, using the Lewis lung carcinoma and C26 colon cancer model, and is accompanied by a reduction in protein synthesis rates of 57% (P < 0.01). Further reduction of mTOR signalling, as seen in Raptor ko animals, leads to a 1.5‐fold increase in autophagic flux (P > 0.001), but does not further increase muscle wasting. On the other hand, activation of Akt–mTORC1 signalling in already cachectic animals completely reverses the 15–20% loss in muscle mass and force (P < 0.001). Interestingly, Akt activation only in skeletal muscle completely normalizes the transcriptional deregulation observed in cachectic muscle, despite having no effect on tumour size or spleen mass. In addition to stimulating muscle growth, it is also sufficient to prevent the increase in protein degradation normally observed in muscles from tumour‐bearing animals.ConclusionsHere, we show that activation of Akt–mTORC1 signalling is sufficient to completely revert cancer‐dependent muscle wasting. Intriguingly, these results show that skeletal muscle maintains its anabolic capacities also during cancer cachexia, possibly giving a rationale behind some of the beneficial effects observed in exercise in cancer patients.

Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via β2-adrenoceptor

β2-adrenoceptor (β2AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through β2AR. The activity of 25 β2AR agonists was measured by β2AR-cAMP response element (CRE) –luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of β2AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of β2AR agonists in activating the β2AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.

FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2-dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes.

BACKGROUND/OBJECTIVESPeroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells.MATERIALS/METHODSC2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2′7′-dichlorofluorescein diacetate assay.RESULTSGPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2.CONCLUSIONSThe results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

FGF-2-Dependent Signaling Activated in Aged Human Skeletal Muscle Promotes Intramuscular Adipogenesis

Abstract Background: A unique feature of muscle during aging, obesity and type 2 diabetes is the appearance of adipose tissue between skeletal muscle fibers, the intramuscular adipose tissue (IMAT). IMAT is generally associated with systemic insulin resistance, decreased muscle strength and, in older adults, impaired mobility. A large body of work over the last years have addressed the origin of IMAT. Skeletal muscle contains preadipocyte progenitors termed fibro/adipogenic progenitors (FAPs) that normally do not form adipocytes, but proliferate during muscle injury to support the commitment of myogenic progenitor cells during muscle repair. However, under the conditions outlined above, FAPs differentiate to adipocytes and give rise to IMAT. The molecular cues that trigger this pathogenesis are unknown and strategies that can modulate the fate of FAPs and their propensity to differentiate to adipocytes in disease states are urgently needed. Methods: We have used molecular cloning and genome editing techniques together with a variety of biochemical, molecular, genomic, transcriptomic and proteomic analyses in pre-adipocyte and muscle cell lines, primary cells isolated from human and mouse skeletal muscle, human skeletal muscle biopsies, and animal models. Results: Using multiple screening assays upstream and downstream of a master regulator of myogenesis, microRNA (miR)-29a, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. We identified FGF-2 as an upstream regulator that increases miR-29a promoter activity and gene expression via MEK1/2/MAPK signaling and consequently decreases the conserved miR-29a target SPARC. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. CRISPR/Cas9-mediated genomic deletions of miR-29a recognition elements located in the Sparc 3′UTR of muscle cells and AAV-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of FAPs in vitro and IMAT formation in vivo. Skeletal muscle from human donors aged &amp;gt; 75 years versus &amp;lt; 55 years showed activation of FGF-2-dependent signaling and increased IMAT. Conclusion: FGF-2 not only stimulates muscle growth, but also promotes intramuscular adipogenesis via targeting the fate of FAPs. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a novel pathway, which has the potential to provide innovative diagnostic and therapeutic approaches to combat fat accumulation in aged human skeletal muscle.

A Comparison Between Total Body and Split Routine Resistance Training Programs in Trained Men.

Bartolomei, S, Nigro, F, Malagoli Lanzoni, I, Masina, F, Di Michele, R, and Hoffman, JR. A comparison between total body and split routine resistance training programs in trained men. J Strength Cond Res 35(6): 1520-1526, 2021-The purpose of the present investigation was to compare the effects of total body (TB) versus split routine (SR) resistance training workouts on maximal strength and muscle hypertrophy in trained men. Twenty-one resistance-trained men were randomly assigned to either a TB (TB: age = 24.1 ± 4.4 years; body mass = 78.7 ± 11.3 kg; body height = 177.0 ± 3.9 cm) or the SR group (SR: age = 24.9 ± 4.2 years; body mass = 79.2 ± 9.5 kg; body height = 175.2 ± 6.0 cm). Both groups performed a 10-week resistance training program. Isokinetic bench press at 75 and 25 cm·s-1 (ISOK75 and ISOK25, respectively), isometric bench press (ISOBP), isometric squat (ISOSQ), and one repetition maximum BP and SQ assessments were performed before and after training. Muscle thickness of the pectoralis major (PECMT), superior part of trapezius (TRAPMT), and vastus lateralis (VLMT) muscles was also evaluated at the same timepoints using ultrasonography. Improvements were observed in both groups for all strength assessments and muscle thicknesses. Only changes in ISOK25 were significantly (p = 0.015) greater in TB than in SR, while significantly greater (p = 0.037) changes in VLMT were detected in SR compared with TB. Results indicated that a TB training paradigm may be more appropriate for maximal strength improvement, while an SR training protocol may be more optimal in stimulating muscle growth in experienced, resistance-trained men.

Anabolic-androgenic steroids (AAS) users on AAS use: Negative effects, ‘code of silence’, and implications for forensic and medical professionals

Anabolic-androgenic steroids (AAS) are image and performance enhancing drugs (IPEDs) that can improve endurance and athletic performance, reduce body fat and stimulate muscle growth. The use of steroids has been studied in the medical and psychological literature, in the sociology of sport, health and masculinity, and relatively recently in criminology. Whilst there is significant medical and psychological evidence on the short term and longer side effects of AAS, there is surprisingly very little evidence based on the users' perception of the negative aspects of AAS use. Drawing on ethnographic research conducted in a locale in the Northeast of England and additional interviews with 24 AAS users, the article offers an account of the negatives aspects of AAS as put forwards by users (acne, abscess, and mood alterations), and highlights the ‘code of silence’ that exists around AAS use. This ‘code’ makes AAS users a ‘hard-to-reach’ group for medical professionals. By listening to the participants' perspectives, forensic and medical professionals can be better informed towards monitoring and reducing harms from AAS.