Exercise-induced Muscle Hypertrophy Research Articles

Bioavailable testosterone and androgen receptor activation, but not total testosterone, are associated with muscle mass and strength in females.

Testosterone, the major androgen, influences the reproductive and non-reproductive systems in males and females via binding to the androgen receptor (AR). Both circulating endogenous testosterone and muscle AR protein content are positively associated with muscle mass and strength in males, but there is no such evidence in females. Here, we tested whether circulating testosterone levels were associated with muscle mass, function, or the muscle anabolic response to resistance training in pre-menopausal females. Twenty-seven pre-menopausal, untrained females (aged 23.5 ± 4.8 years) underwent a 12-week resistance training programme. Muscle strength, size, power, and plasma and urine androgen hormone levels were measured. Skeletal muscle biopsies were collected before and after the training programme to quantify the effect of resistance training on AR content and nuclear localisation. Primary muscle cell lines were cultured from a subset (n=6) of the participants' biopsies and treated with testosterone to investigate its effect on myotube diameter, markers of muscle protein synthesis and AR cellular localisation. Physiological levels of total testosterone were not associated with muscle mass or strength at baseline or with the changes in muscle mass and strength that occurred in response to resistance training in our cohort of pre-menopausal females. In contrast, bioavailable testosterone and the proportion of nuclear-localised AR were positively associated with skeletal muscle mass and strength in pre-menopausal females. In vitro, supra-physiological doses of testosterone increased myocyte diameter, but this did not occur via the Akt/mTOR pathway as previously suggested. Instead, we show a marked increase in AR nuclear localisation with testosterone administration in vitro. KEY POINTS: Total circulating testosterone was not related to muscle mass or strength before or after resistance training in pre-menopausal females. Bioavailable testosterone was positively related to exercise-induced muscle hypertrophy in pre-menopausal females. In vivo nuclear localisation of the androgen receptor was positively related to muscle mass in pre-menopausal females at baseline, but not to resistance training-induced hypertrophy. Testosterone treatment induced androgen receptor nuclear translocation but did not induce mTOR signalling in primary skeletal myocytes cultured from pre-menopausal female muscle.

Hormones, Hypertrophy, and Hype: An Evidence-Guided Primer on Endogenous Endocrine Influences on Exercise-Induced Muscle Hypertrophy.

We review the evidence indicating that endogenous changes in these hormones, including testosterone, growth hormone, insulin growth factor-1, and estrogen, and their proposed anabolic effects contribute to and augment resistance exercise training (RET)-induced hypertrophy. Additionally, we provide recommendations for gold-standard methodological rigor to establish best practices for verifying menstrual phases as part of their research, ultimately enhancing our understanding of the impact of ovarian hormones on RET-induced adaptations.

Genome-wide association study of exercise-induced skeletal muscle hypertrophy and the construction of predictive model.

The aim of the current study was to investigate interindividual differences in muscle thickness of the rectus femoris (MTRF) following 12 wk of resistance training (RT) or high-intensity interval training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-wk exercise period. A genome-wide association study was used to identify variants associated with the MTRF response, separately for RT and HIIT. Using the polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for the MTRF response were constructed using random forest (RF), support vector mac (SVM), and generalized linear model (GLM) in 10 cross-validated approaches. MTRF increased significantly after both RT (8.8%, P < 0.05) and HIIT (5.3%, P < 0.05), but with considerable interindividual differences (RT: -13.5 to 38.4%, HIIT: -14.2 to 30.7%). Eleven lead single-nucleotide polymorphisms in RT and eight lead single-nucleotide polymorphisms in HIIT were identified at a significance level of P < 1 × 10-5. The PPS was associated with the MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance compared with RF models (P < 0.05), and the GLM demonstrated optimal performance with an area under curve of 0.809 (95% confidence interval: 0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.NEW & NOTEWORTHY The interindividual variability induced muscle hypertrophy by resistance training (RT) or high-intensity interval training (HIIT) and the associated genetic architecture remain uncertain. We identified genetic variants that underlie RT- or HIIT-induced muscle hypertrophy and established them as pivotal factors influencing the response regardless of the training type. The genetic-phenotype predictive model developed has the potential to identify nonresponders or individuals with low responsiveness before engaging in exercise training.

The Role of PRMT1 in Skeletal Muscle Hypertrophy: A Research Protocol

Introduction: Protein arginine methyltransferases (PRMTs) are an important class of enzymes that catalyze post-translational modification of arginine residues on histone or nonhistone substrates. In skeletal muscle, PRMT1 expression has been linked to muscle homeostasis, regeneration, metabolism, and synthesis. The expression of PRMT1 in skeletal muscle has already been shown to be induced by treadmill exercise, however, the relationship between PRMT1 and skeletal muscle hypertrophy remains unexplored. This study aims to determine the significance of PRMT1 in muscle hypertrophy by identifying whether wild-type mice (WT) experience elevated levels of exercise-induced muscle hypertrophy compared to PRMT1-knockout mice (KO). Methods: 12-month-old mice will be split into male (M) and female (F) groups. Both M and F groups will then be randomly distributed to WT and KO groups. WT M, KO M, WT F, and KO F groups will be further randomly divided into sedentary (SED) and exercise (EX) groups. EX groups will undergo a resistance training program for 8 weeks while SED groups will be at rest. All mice will be euthanized by cervical dislocation while at rest by the end of the 8 weeks, and their tissue samples will be collected. The progression of muscle hypertrophy between groups will be assessed weekly using Bioseb grip strength tests in grams normalized to body mass in grams (g/g). Following the 3 months, muscle biopsies of the gastrocnemius (GAS) muscle will be taken to perform fluorescence staining of the myofibers. Primary and secondary antibodies against myosin heavy chains I, IIa, IIx, and IIb will be used to stain cross-sectional areas (CSA). The CSA of the fast-glycolytic fibers will be measured to quantify muscle hypertrophy between WT and KO groups. Anticipated Results: The Bioseb grip strength tests and GAS immunostaining should demonstrate that WT mice have greater grip strength and myofibers with larger CSAs compared to KO mice. Conclusion: These results would demonstrate the importance of PRMT1 in facilitating exercise-induced muscle hypertrophy. Future directions may involve exploring downstream signaling molecules of PRMT1 to identify potential PRMT1 up regulators, accelerating muscle hypertrophy and combating pathological muscle atrophy.

Beyond Mechanical Tension: A Review of Resistance Exercise-Induced Lactate Responses & Muscle Hypertrophy.

The present review aims to explore and discuss recent research relating to the lactate response to resistance training and the potential mechanisms by which lactate may contribute to skeletal muscle hypertrophy or help to prevent muscle atrophy. First, we will discuss foundational information pertaining to lactate including metabolism, measurement, shuttling, and potential (although seemingly elusive) mechanisms for hypertrophy. We will then provide a brief analysis of resistance training protocols and the associated lactate response. Lastly, we will discuss potential shortcomings, resistance training considerations, and future research directions regarding lactate’s role as a potential anabolic agent for skeletal muscle hypertrophy.

Therapeutic Sources of Skeletal Muscle Regeneration from Volumetric Muscle Loss: A Narrative Review

PURPOSE: Minor skeletal muscle injuries can be repaired, but more extensive volumetric muscle loss (VML) leads to a permanent functional disability with ambiguous therapeutic outcomes, and reconstructive surgical procedures are constrained by donor tissue scarcity. This review assessed the considerable attention paid to biomaterials in healing damaged skeletal muscle.METHODS: A comprehensive search in PubMed, Web of Science, Google Scholar, and Wiley Online Library was conducted to obtain previous studies exploring the state of biocompatible tissue scaffolds for VML recovery.RESULTS: By regenerating the function of damaged skeletal muscle, tissue-engineered skeletal muscle construction could revolutionize the treatment of VML. However, transporting cells into the wounded muscle location presents a significant challenge because it may result in unfavorable immunological reactions. The development and validation of several biomaterials with varying physical and chemical natures to treat various muscle injuries have recently been undertaken to overcome this problem. This review discusses the relative benefits of satellite cells (SC), the most prevalent skeletal muscle stem cells employed to seed scaffolds.CONCLUSIONS: Biomaterials can be used with skeletal muscle stem cells and growth factors to repair VML because of their customizable and desirable physicochemical qualities. Owing to the capacity of SCs for self-renewal and their undifferentiated state, these cells are excellent candidates for cell therapy. A large gap exists between understanding SC behavior and how it can be used to repair and regenerate human skeletal muscle tissue. Thus, this review sought to portray the current knowledge on the lifespan of SCs and their involvement in exercise-induced muscle regeneration and hypertrophy.

Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models-Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)-/-, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)-/-, and Pax7-Arl3-/--by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3-/- mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3-/- and Pax7-Arl3-/- mice or primary isolated Myf5-Arl3-/- and Pax7-Ift88-/- myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.

運動による骨格筋肥大メカニズム

骨格筋は可塑性に富んだ組織であり，物理・化学（代謝）的環境の変化に応じて機能・形態的に順応する．たとえば，筋力トレーニングのような過負荷によって筋肥大や筋力の増加が生じる．反対に，寝たきりなどの不活動によって筋萎縮や筋力の低下が生じる．骨格筋は運動器としてのみならず代謝臓器としても重要な役割を果たすことから，その機能・量調節メカニズムの理解はわれわれの健康維持増進を図るうえで重要な基盤となる．本稿では，運動による骨格筋肥大の分子機構について，タンパク質代謝調節機構を中心に最新の知見を紹介する．

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

Sedentary and Trained Older Men Have Distinct Circulating Exosomal microRNA Profiles at Baseline and in Response to Acute Exercise.

Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men (n = 5) and age-matched sedentary males (n = 5) at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Following the isolation and enrichment of exosomes from plasma, exosome-enriched preparations were characterized and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed by comparing the baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. While further validation is needed, including measurements of IGF-1/IGF-1 signaling in blood or skeletal muscle, our results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.

Response of Resistance Exercise-Induced Muscle Protein Synthesis and Skeletal Muscle Hypertrophy Are Not Enhanced After Disuse Muscle Atrophy in Rat.

Skeletal muscle disuse rapidly decreases muscle mass. Resistance training (RT) is believed as the most effective way to gain muscle mass via an increase in mTORC1 activity and muscle protein synthesis (MPS). However, it remains unclear whether muscle atrophy by disuse alters the mTORC1 activation and MPS response to an acute resistance exercise (RE) and chronic RT–mediated skeletal muscle hypertrophy. This study investigated the influence of disuse muscle atrophy on the response of mTORC1 activation and MPS to an acute RE. We also evaluated whether disuse muscle atrophy affects the response of RT-induced muscle mass gain. Thirty male Sprague-Dawley rats were randomly divided into control (CON) or hindlimb suspension (HS) groups. A 14-day HS via the tail was used as the model for gastrocnemius muscle disuse in the HS group. Unilateral lower limb muscle contraction using by percutaneous electrical stimulation was used to mimic the stimuli of RE. Ten bouts of RE were performed in 3-week as chronic RT. Our results showed that MPS and mTORC1 activity was unchanged after HS at basal state. However, the ribosomal RNA (rRNA) level was reduced in HS rats compared to that in CON rats at basal state. MPS and rRNA increased in both HS and CON rats in response to acute RE to the same extent. However, the level of mTORC1 activation in response to an acute RE was significantly higher in HS than that in the CON group at 12 h after exercise, even though no difference was observed at 3 h after exercise. The 10-bout RT significantly increased gastrocnemius muscle mass in both CON and HS rats. The response of muscle hypertrophy did not differ between the groups. Therefore, MPS in response to acute RE and muscle hypertrophy in response to chronic RT were unaltered after disuse muscle atrophy.

Magnitude and Composition of the Energy Surplus for Maximizing Muscle Hypertrophy: Implications for Bodybuilding and Physique Athletes

ABSTRACT This review aimed to explore the nature of energy consumption for optimizing muscle growth in the presence of a resistance training program with a specific focus on implications for bodybuilders and physique athletes. Although gains in muscle mass can be achieved when resistance training is performed under hypocaloric conditions, research indicates that maximizing exercise-induced muscle hypertrophy requires an energy surplus. Herein, we discuss the interplay between total dietary energy intake and macronutrient ratios, and provide evidence-based guidelines as to how they should be manipulated to optimize muscular adaptations.

Automated assessment of regional muscle volume and hypertrophy using MRI

This study aimed to validate a fully automatic method to quantify knee-extensor muscle volume and exercise-induced hypertrophy. By using a magnetic resonance imaging-based fat-water separated two-point Dixon sequence, the agreement between automated and manual segmentation of a specific ~15-cm region (partial volume) of the quadriceps muscle was assessed. We then explored the sensitivity of the automated technique to detect changes in both complete and partial quadriceps volume in response to 8 weeks of resistance training in 26 healthy men and women. There was a very strong correlation (r = 0.98, P < 0.0001) between the manual and automated method for assessing partial quadriceps volume, yet the volume was 9.6% greater with automated compared with manual analysis (P < 0.0001, 95% limits of agreement −93.3 ± 137.8 cm3). Partial muscle volume showed a 6.0 ± 5.0% (manual) and 4.8 ± 8.3% (automated) increase with training (P < 0.0001). Similarly, the complete quadriceps increased 5.1 ± 5.5% with training (P < 0.0001). The intramuscular fat proportion decreased (P < 0.001) from 4.1% to 3.9% after training. In conclusion, the automated method showed excellent correlation with manual segmentation and could detect clinically relevant magnitudes of exercise-induced muscle hypertrophy. This method could have broad application to accurately measure muscle mass in sports or to monitor clinical conditions associated with muscle wasting and fat infiltration.

Effect of a High Fat and High Protein Diet on Exercise-Induced Skeletal Muscle Hypertrophy in Rats

The skeletal muscle mass varies by race. Dietary habits over generations are a factor that influences the skeletal muscle mass, as well as genetic factors. Therefore, we investigated the effects of diets with different macronutrient contents on exercise-induced muscle hypertrophy in rats. Male 4-week-old Sprague–Dawley rats were randomly divided into three groups: a normal-diet (N), high-protein diet (HP) and high-fat diet (HF) group. The food intake was manipulated to gain comparable body weight across the three groups. All rats were performed a climbing training exercise for 8 weeks. The final body weight and weight of the liver, kidneys and adipose tissues did not significantly differ among the groups. The flexor hullucis lingus was significantly higher in the HF group than in the HP group. The total lipid content in the muscle was significantly higher in the HF group than in the N group, while it did not differ significant between the HF and HP groups. There were no marked differences in the water or protein content in the muscle among the groups. The plasma amino acid concentration was significantly or tended to be lower in the HP group than in the HF or N group, except for the branched-chain amino acid concentration, which tended to be higher after ingesting the HP diet than other diets. These findings suggest that consuming an HP diet is not likely to facilitate exercise-induced muscle hypertrophy, partly due to the plasma amino acid imbalance induced by habitual HP diet consumption.

Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining.

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed "muscle memory." The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. We hypothesized that myonuclei acquired during training-induced hypertrophy would remain following loss of muscle mass with detraining. Singly housed female C57BL/6J mice performed 8 wk of PoWeR, while another group performed 8 wk of PoWeR followed by 12 wk of detraining. Age-matched sedentary cage-dwelling mice served as untrained controls. Eight weeks of PoWeR yielded significant plantaris muscle fiber hypertrophy, a shift to a more oxidative phenotype, and greater myonuclear density than untrained mice. After 12 wk of detraining, the plantaris muscle returned to an untrained phenotype with fewer myonuclei. A finding of fewer myonuclei simultaneously with plantaris deconditioning argues against a muscle memory mechanism mediated by elevated myonuclear density in primarily fast-twitch muscle. PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and our findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.

Oral Supplementation Using Gamma-Aminobutyric Acid and Whey Protein Improves Whole Body Fat-Free Mass in Men After Resistance Training.

BackgroundOral gamma-aminobutyric acid (GABA) supplementation increases growth hormone (GH) serum levels and protein synthesis. Therefore, post-exercise supplementation using GABA and protein may help enhance training-induced muscle hypertrophy. We evaluated whether GABA with whey protein enhanced muscular hypertrophy in men after progressive resistance training.MethodsTwenty-one healthy men (26 - 48 years) were randomized to receive whey protein (WP; 10 g) or whey protein + GABA (WP + GABA; 10 g + 100 mg) daily for 12 weeks. Both groups performed resistance training twice per week (three sets of 12 repetitions at 60% of maximal strength; leg press, leg extension, leg curl, chest press, and pull down). Body composition was assessed using dual-energy X-ray absorptiometry.ResultsIn the WP + GABA group, resting plasma GH concentrations were significantly elevated at 4 and 8 weeks, compared to baseline. However, resting plasma GH concentrations in the WP group were only significantly elevated at 8 weeks. After 12 weeks, the WP + GABA group exhibited significantly greater increase in whole body fat-free mass than the WP group.ConclusionsThe GABA and whey protein combination was more effective for increasing whole body fat-free mass; daily GABA supplementation may help enhance exercise-induced muscle hypertrophy.

Impact of drugs with anti-inflammatory effects on skeletal muscle and inflammation: A systematic literature review.

Ageing-related low-grade inflammation is suggested to aggravate sarcopenia and frailty. This systematic review investigates the influence that drugs with anti-inflammatory effects (AIDs) have on inflammation and skeletal muscle. PubMed and Web of Science were systematically screened for articles reporting the effects of AIDs on inflammation on one hand and on muscle mass and/or performance on the other. Twenty-eight articles were included. These articles were heterogeneous in terms of the subjects studied, intervention components, setting, and outcome measures. Articles on older humans with acute inflammation showed evidence that celecoxib and piroxicam could reduce inflammation and improve performance and that ibuprofen improves exercise-induced muscle hypertrophy and gains in strength. In younger humans, only the effects of AIDs combined with exercise were investigated; no significant benefits of non-selective COX-inhibitors were reported, but improved strength gains with etanercept and reduced muscle soreness with celecoxib were noted. Indomethacin increased acute exercise-induced inflammation and reduced satellite cell differentiation in exercising muscle. Most articles did not systematically report occurrences of side effects. Although AIDs showed significant reduction in inflammation-induced muscle weakness in older hospitalised patients with acute inflammation, robust evidence is still lacking. When combined with exercise, AIDs presented a protective effect against age-related loss of muscle mass, thus enhancing muscle mass and performance. The mechanism regulating muscle strength and its mass seems to differ between individuals of old and young age. However, the effects seem drug-specific and dose-dependent and appear to be influenced by subjects' trainability and the clinical context. In addition, the balance between benefits and harm remains unclear.

Correction to: A mathematical model of the effects of resistance exercise-induced muscle hypertrophy on body composition.

There is a typo in the original equation describing lean mass, and it has also been pointed out to the authors that the model is not strictly energy balanced.

The Hippo Signaling Pathway in the Regulation of Skeletal Muscle Mass and Function.

The Hippo signaling pathway regulates the activity of the proteins Yes-associated protein (Yap) and transcriptional co-activator with PDZ-binding motif (Taz) to control tissue growth in many different cell types. Previously, we demonstrated that Yap is a critical regulator of skeletal muscle mass. We hypothesize that alterations in Yap and Taz activity modulate the anabolic adaptations of skeletal muscle to resistance exercise.

High versus Low doses of Anti-inflammatory Drugs Do Not Differentially Affect Muscle Molecular Response to Acute Resistance Exercise

PURPOSE: We recently reported that high doses of non-steroidal anti-inflammatory drugs (NSAIDs) attenuate resistance exercise-induced muscle hypertrophy in young adults. Yet, little is known about the molecular mechanisms behind this effect. The current study aimed to examine acute muscle molecular responses to resistance exercise during co- ingestion of high and low doses of anti-inflammatory drugs. METHODS: Thirty one young (age 18-35 years) healthy men and women were randomly assigned to daily consumption of high doses of ibuprofen (IBU; 1200 mg; n=15) or low doses of acetylsalicylic acid (ASA; 75 mg; n=16) during an 8-week training intervention. During this period, subjects performed 20 supervised resistance training sessions (4 x 7-12 repetitions) involving the knee extensor muscles. Gene expression and protein signaling of key muscle growth regulators were analyzed from skeletal muscle biopsies obtained before training/treatment and 3 hours after an acute resistance exercise session during week 4 of the intervention. Real-time qPCR procedures were employed to determine mRNA expression. Protein signaling was assessed using western blots. RESULTS: Gene expression of myostatin (0.4-fold; p>0.0005), MuRF-1 (0.8-fold; p=0.015) and FoxO3 (0.6-fold; p>0.0005) decreased in response to the resistance exercise bout, with no difference across groups. Gene expression of IL-6 and STAT3 were unaltered. Protein phosphorylation of p70S6K increased (24-fold, P>0.0005) in response to the resistance exercise bout, with no difference across groups. Protein phosphorylation of STAT3 remained unchanged. CONCLUSIONS: These results show that high and low doses of NSAIDs do not differentially affect exercise-induced changes in gene expression and protein signaling for key markers of muscle growth in young adults. We therefore conclude that these acute markers do not seem to explain the negative effects of high doses of NSAIDs on muscle hypertrophy.