Pax7 mRNA Expression Research Articles

367 Early Fetal to Neonatal Vitamin a Supplementation Improves Growth Performance and Development of Muscle and Pre-Adipocyte in Korean Native Calves

Abstract This study aimed to investigate the effects of vitamin A supplementation during the early fetal to neonatal stages on growth performance, blood metabolites, and the development of muscle and pre-adipocytes in Korean native calves. Twenty female newborn calves [day 0 of age; initial BW: 31.2 kg (SD 3.07)] were stratified based on whether they received vitamin A supplementation during the early fetal to neonatal stages, and then randomly allocated to four groups using a 2 × 2 factorial arrangement. Vitamin A supplementation was conducted as follows: fetal stage (control: 7,800 IU/kg of as-fed, treatment: 22,800 IU/kg of as-fed); neonatal stage (control: 17,000 IU/day, treatment: 53,000 IU/day). Growth performance, blood variables, mRNA expression in muscle tissue, and muscle fiber diameter were evaluated during the experimental period and analyzed using the MIXED procedure with Tukey's test by SAS 9.4 software. As a result, fetal-vitamin A treatment group exhibited higher (P < 0.05) serum vitamin A concentrations and blood glucose concentrations on the day 3 of age. Similarly, vitamin A supplementation in the neonatal stage significantly increased (P < 0.05) serum vitamin A concentrations at day 30 and 60 of age, as well as albumin and glucose concentrations at day 60 of age. Moreover, both birth and weaning BW were significantly greater (P < 0.05) in calves receiving vitamin A supplementation during the fetal stage. However, feed intake and muscle fiber diameter showed no differences (P > 0.05) between the groups. In addition, supplementation of vitamin A during the fetal stage resulted in upregulation (P < 0.05) of ZNF423 mRNA expression in the longissimus dorsi muscle, whereas neonatal supplementation upregulated (P < 0.05) the mRNA expression of PAX7 and MYF5. Our findings suggested that vitamin A supplementation during the early fetal to neonatal stages can enhance the growth performance of offspring calves and potentially promote an increase in pre-adipocyte and satellite cell storage in muscle tissue. This information can be applied in integrated fetal-neonatal nutrient feeding strategies in beef cattle.

252 Use of Agomir and Antagomir Technologies to Alter Mirna Expression and Muscle Hypertrophy in Intrauterine Growth Restricted Lambs

Abstract microRNAs (miRNA) are present in skeletal muscle and play important roles in regulating gene expression. Previous research identified miR-22-3p and miR-127 as differentially regulated during muscle hypertrophy and in vitro experiments found that antagomir-22-3p and mimic-127 enhanced satellite cell proliferation. The objective of this study was to test in vivo intramuscular injection of agomiR-127 or antagomir-22-3p in the longissimus muscle (LM) on miRNA and target mRNA expression in intrauterine growth restricted lambs. Pregnant ewes (n = 18) with twins were nutrient restricted (60%) from gestational d 85 to parturition. On d 2 of age, lambs were randomly selected and assigned to one of two miRNA treatments, 1) agomiR-127 (AGO127, 100 nM, n = 9) to assess gain of function or 2) antagomiR-22-3p (ANT22, 500 nM, n = 9) to assess loss of function. AgomiR and antagomiR technologies are chemically modified miRNA mimics or inhibitors that do not require transfection for in vivo use. AgomiR-127 or antagomir-22-3p were reconstituted in phosphate buffered saline (PBS) and injected into the center of the LM on the left side every 3-d starting at the 10th rib and moving posterior by 1.27 cm at each injection for a total of 7 injections. A sham control treatment (SHAM127 or SHAM22) of PBS was administered following the same protocol in the right LM to serve as the in-animal control. Lambs were harvested 4 d after the last injection and samples were collected from the injection region of each LM for miRNA and mRNA expression, histology, and proteomic analyses. Data were analyzed using paired t-tests to compare each miRNA treatment to its SHAM within animal. AGO127 up-regulated (P = 0.0071) miR-127 expression compared with SHAM127. mRNA expression of PAX7 and MSTN were up-regulated (P < 0.05) and IGFBP2 expression was down-regulated (P < 0.05) for AGO127 compared with SHAM127. Both protein and DNA content of AGO127 were increased (P < 0.05) but the ratio of protein to DNA did not change (P > 0.05). Proteomic analyses found 11 proteins that were differentially expressed for AGO127 compared with SHAM127. ANT22 down-regulated (P = 0.0024) miR-22-3p expression from SHAM22. Expression of predicted mRNA targets of miR-22-3p (ACVR2a, ACVR2b, SIRT1), myosin heavy chain isoforms (MyHCI, MyHCIIa, MyHCIIx), and other myogenic genes (MAPK6, IGF1, MyoG) were also altered (P < 0.05) in the LM compared with SHAM22. DNA content and the protein to DNA ratio was greater (P < 0.05) in ANT22 than SHAM22. Proteomic analyses identified nine proteins that were differentially expressed (P < 0.05) for ANT22. The direct injection of agomiR and antagomir technologies in the LM up- and down-regulated expression, respectively, for the miRNA of interest, which altered mRNA expression of predicted targets, protein abundance and muscle fiber type.

Low-intensity pulsed ultrasound and parathyroid hormone improve muscle atrophy in estrogen deficiency mice

Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality. Low-intensity pulsed ultrasound (LIPUS) is an acoustic wave inducing biological effects mainly by the mechanical stimulation and used as a non-invasive physical therapy for muscle repair. Parathyroid hormone (PTH) is an 84-amino-acid polypeptide, and its bioactive fragment [PTH (1–34)] has potential application in the treatment of MA. We speculate that the combination of physical therapy (i.e., the LIPUS) and regulatory hormone (i.e., the PTH) would be more effective in the treatment of MA. The objective of this study was to evaluate the individual and combined effects of LIPUS and PTH therapy on MA in estrogen deficiency mice. Seventy 8-week-old female C57BL/6J mice were used in this study and the MA model was induced by an intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD) for 20 consecutive days. The VCD-induced MA mice were randomly divided into MA, LIPUS, PTH and LIPUS + PTH (Combined) groups (n = 10/group). In the LIPUS group, the mice were treated by LIPUS in bilateral quadriceps muscles for 20 min, five times a week for 6 weeks. In the PTH group, the mice received subcutaneous injection of PTH (1–34) (80 ug/kg/d) five times a week, for 6 weeks. In the Combined group, the PTH was administrated 30 min before each LIPUS session. Hematoxylin-eosin (H&E) staining, serum biochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to evaluate the therapeutic effects of related treatments. The results showed that the MA mice had a disordered estrus cycle, significantly decreased muscle mass and myofibers cross-sectional area (CSA). After treatments, LIPUS, PTH and Combined groups had a significantly increased CSA, compared with the MA mice without treatment. In addition, Combined group had a significantly increased mRNA expression of Pax7, MyoD and MyoG, compared with LIPUS and PTH monotherapy groups. Our findings indicated that the combination of LIPUS and PTH treatment improves muscle regeneration ability, which might have potential for treating MA in postmenopausal women.

Higher frequency electrical stimulation enhanced myloglossus satellite cell differentiation by upregulating expression of Pax7 mRNA, MyoD, myogenin and MyHC protein.

We investigated the effect of electrical stimulation (ES) of varying pulse frequency on differentiation and proliferation of canine myloglossus satellite cells in vitro. Cellular viability and proliferation were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometry fluorescence-activated cell sorting analysis. Cellular differentiation and expression of mark molecule were assayed by Real Time-PCR and Western blot. With increasing frequency ES, we found a significant increase in Myod (r=0.988, p<0.0001), myogenin (r=0.988, p<0.0001), MyHC-slow (r=0.988, p<0.0001), MyHC-fast (r=0.875, p<0.0001) protein expression, and Pax7 mRNA expression (r=0.712, p=0.001). Pax7 mRNA expression and MyoD, myogenin, and MyHC protein expression were increased with increment of electrical stimulation frequency in myloglossus muscle satellite. Higher frequency ES enhanced myloglossus satellite cell differentiation, not proliferation and viability.

Mitochondrial dysfunction and consequences in calpain-3-deficient muscle

BackgroundNonsense or loss-of-function mutations in the non-lysosomal cysteine protease calpain-3 result in limb-girdle muscular dystrophy type 2A (LGMD2A). While calpain-3 is implicated in muscle cell differentiation, sarcomere formation, and muscle cytoskeletal remodeling, the physiological basis for LGMD2A has remained elusive.MethodsCell growth, gene expression profiling, and mitochondrial content and function were analyzed using muscle and muscle cell cultures established from healthy and calpain-3-deficient mice. Calpain-3-deficient mice were also treated with PPAR-delta agonist (GW501516) to assess mitochondrial function and membrane repair. The unpaired t test was used to assess the significance of the differences observed between the two groups or treatments. ANOVAs were used to assess significance over time.ResultsWe find that calpain-3 deficiency causes mitochondrial dysfunction in the muscles and myoblasts. Calpain-3-deficient myoblasts showed increased proliferation, and their gene expression profile showed aberrant mitochondrial biogenesis. Myotube gene expression analysis further revealed altered lipid metabolism in calpain-3-deficient muscle. Mitochondrial defects were validated in vitro and in vivo. We used GW501516 to improve mitochondrial biogenesis in vivo in 7-month-old calpain-3-deficient mice. This treatment improved satellite cell activity as indicated by increased MyoD and Pax7 mRNA expression. It also decreased muscle fatigability and reduced serum creatine kinase levels. The decreased mitochondrial function also impaired sarcolemmal repair in the calpain-3-deficient skeletal muscle. Improving mitochondrial activity by acute pyruvate treatment improved sarcolemmal repair.ConclusionOur results provide evidence that calpain-3 deficiency in the skeletal muscle is associated with poor mitochondrial biogenesis and function resulting in poor sarcolemmal repair. Addressing this deficit by drugs that improve mitochondrial activity offers new therapeutic avenues for LGMD2A.

Effects of replacing fish oil with palm oil in diets of Nile tilapia (Oreochromis niloticus) on muscle biochemical composition, enzyme activities, and mRNA expression of growth-related genes

BackgroundDue to the continuous demand for fish coupled with decline in capture fisheries, there is the need to increase aquaculture production to meet the demand. Aquaculture is faced with high cost of feeding since fish oil and fish meal are expensive. In view of this, there are calls to explore alternatives that are cheap and reliable.ObjectivesThis study on Oreochromis niloticus was conducted to evaluate the effects of replacing fish oil (FO) with palm oil (PO) at 0%, 25%, 50%, 75%, and 100% on muscle fatty acid and proximate composition as well as growth-related enzyme activities and mRNA expression.MethodsOreochromis niloticus were fed five experimental diets (33% crude protein and 10% crude lipid) for 8 weeks. Feed had variation in fish oil and palm oil contents. After the 8 weeks feeding trial, five fish were sampled from each tank (15 from each treatment) and euthanized using an excess dose of tricaine methane sulfonate (MS-222 at 200 mg/L). Fatty acid and enzyme activities were analyzed using standard protocols. Also, RT-qPCR was used to quantify the expression levels of selected growth-related genes.ResultsFish fed 25% PO recorded the least muscle protein content and was significantly lower than the group fed 100% PO. Paired box protein 7 (Pax-7) enzyme activity was significantly higher in the group fed 50% PO compared to the groups fed 25% PO and 100% PO, while caplain-3 (Capn-3) was significantly lower in the group fed 0% PO compared to all other groups. There was a significant difference among treatments with respect to mRNA expression of Pax-7 and Capn-3. Group fed 25% PO had significantly lower mRNA expression of Pax-7, while the group fed 75% PO recorded significantly higher mRNA expression of Capn-3 compared to groups fed 0% PO, 25% PO, and 100% PO. Pearson’s correlation analysis revealed that Igf-I and Igf-II mRNA expression have significant correlation with n-3 polyunsaturated fatty acids content in muscle.ConclusionThe results suggest muscle protein content could be modified if FO is replaced with PO. Also, mRNA expression of Pax-7 and Capn-3 is affected by replacing FO with PO.

In ovo feeding of creatine pyruvate alters energy reserves, satellite cell mitotic activity and myogenic gene expression of breast muscle in embryos and neonatal broilers

We investigated the effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on energy reserves, satellite cell mitotic activity (SCMA) and myogenic gene expression in breast muscle of embryos and neonatal broilers. A total of 960 eggs were randomly allocated into three treatments: 1) non-injected control group, 2) saline group injected with 0.6 mL of physiological saline (0.75%), and 3) CrPyr group injected with 0.6 mL of physiological saline (0.75%) containing 12 mg CrPyr/egg at 17.5 d of incubation. After hatching, a total of 120 male chicks were randomly assigned to each treatment group, with eight replicate sets per group. Selected chicks had body BW close to the average of their pooled group. Our results showed that the total and relative breast muscle weights of broilers subjected to CrPyr treatment were higher than those in the control and saline groups on 19 d of incubation (19 E), the day of hatch, 3 and 7 d post-hatch (P < 0.05). The myofiber diameter and cross-sectional area of individuals in the CrPyr group were higher than those in other treatments on 3 and 7 d post-hatch (P < 0.05). Moreover, IOF of CrPyr increased (P < 0.05) creatine concentrations on 19 E, the day of hatch and 3 d post-hatch, the same treatment increased phosphocreatine concentrations on 19 E. Broilers in the CrPyr group showed higher expression of myogenic differentiation 1 (MyoD) (P < 0.05), myogenin and paired box 7 (Pax7), as well as higher index of SCMA on 3 d post-hatch. However, myostatin mRNA expression in CrPyr-treated broilers was down-regulated on 3 d post-hatch (P < 0.05). These results indicated that IOF of CrPyr increased energy reserves of embryos and SCMA of broilers on 3 d post-hatch, which led to enhanced muscle growth in the late embryos and neonatal broilers. Additionally, IOF of CrPyr increased the activity of satellite cells possibly through up-regulating MyoD, myogenin, and Pax7 mRNA expression and down-regulating myostatin mRNA expression.

Molecular cloning, characterisation and functional analysis of the duck Forkhead box O3 (FOXO3) gene

1. The Forkhead box O3 (FOXO3) transcription factor is a crucial regulator of cell fate that controls proliferation, apoptosis and differentiation. However, the role of FOXO3 regulation in duck myoblasts is not fully understood.2. The aim of this study was to clone and determine the complete coding sequence (CDS) of the duck FOXO3 gene and to assess its function in myoblasts.3. Primers specific for the predicted duck FOXO3 gene were designed using the public mallard duck reference sequence in GenBank. The CDS was cloned by RT-PCR and double digested to generate the expression vector pEGFP-N1-FOXO3.4. Sequence analysis showed that the full-length FOXO3 CDS is 1467 bp, encoding 488 amino acids and is highly conserved across many bird species. Amino acid sequence analysis revealed a DNA-binding domain (aa 1–77).5. Myoblast transfection with pEGFP-N1-FOXO3 showed that FOXO3 mRNA expression at 24 h was elevated in pEGFP-N1-FOXO3-transfected myoblasts compared to pEGFP-N1-transfected cells or controls. MRF4, MyoD, MyoG, Myf5 and PAX7 mRNA expression in the pEGFP-N1-FOXO3 group was lowest. However, myostatin (MSTN) and PAX3 mRNA expression did not differ.6. These results suggest that FOXO3 plays a critical role in the proliferation and differentiation of duck myoblasts.

Early myogenic responses to acute exercise before and after resistance training in young men.

To enable dynamic regulation of muscle mass and myofiber repair following injury, a satellite cell precursor population exists to supply additional nuclei. Activated satellite cells express many genes and associated proteins necessary for maturation and incorporation into the damaged fiber. There is little knowledge about the response of these markers following whole-body resistance exercise training. We investigated the impact of 12 weeks of progressive whole-body resistance training on the expression of MRFs, PAX7, NCAM, and FA1, incorporating both acute and chronic resistance exercise components. Ten young recreationally active males (21.2 ± 3.5 years) performed 12 weeks of whole-body resistance training at 70–85% of their predetermined one-repetition maximum (1RM). At the initiation and completion of the training period, muscular strength was assessed by RM and dynamometer testing, and vastus lateralis samples were obtained prior to and 3 h following an acute resistance exercise test (both whole-body and isometric exercises). Increased mRNA expression of PAX7 (threefold), NCAM (threefold), MYF5 (threefold), MYOD (threefold) and MYOGENIN (twofold) was observed 3 h after the acute resistance exercise test, both pre and posttraining. Similarly, PAX7 (11-fold) and FA1 (twofold) protein abundance increased after acute exercise, while resting NCAM (eightfold) and FA1 (threefold) protein abundance increased following 12 weeks of resistance training. It is possible that these molecular changes are primarily due to the preceding exercise bout, and are not modified by long-term or whole-body exercise training.

Age-related changes in satellite cell proliferation by compensatory activation in rat diaphragm muscles

To investigate the age-related changes in satellite cell (SC) proliferation in vivo, we used a compensatory activation (CAC) model of the hemi-diaphragm muscle. Young (2-month), adult (14-month) and old (24-month) rats were randomly divided into control and CAC groups. In the CAC group, denervation surgery in the left hemi-diaphragm was performed to induce CAC of the right hemi-diaphragm. Six days after the surgery, the CAC diaphragm muscle was removed and separated into two blocks for immunohistochemical staining and real time RT-PCR procedures. The number of SCs in type I and IIa fibers were not affected significantly by the CAC in any age groups, but that in type IIx/b fibers was significantly increased in the young and adult groups. As compared to the age-matched control group, the Pax7 mRNA expression level was significantly higher in the young and adult CAC groups, but not in the old CAC group. These results may suggest that the mechanism of SC proliferation in type IIx/b fibers is impaired in aged diaphragm muscles.

Age-related Changes In Pax7 mRNA Expression In The Rat Activated Diaphragm

PURPOSE: Satellite cells are muscle stem cells capable of increasing myonuclear number relative to the degree of muscle fiber hypertrophy. To investigate whether satellite cell activation in aged animals is impaired in response to increased activity, we used a compensatory activation model in the rat hemi-diaphragm muscle. METHODS: Young (8∼12 weeks) and old (24∼30 months) rats were randomly divided into control (CTL) and compensatory activation (CAC) groups. In the CAC group, denervation surgery in the left hemi-diaphragm was performed to induce CAC of the right hemi-diaphragm. Six days after surgery, the CAC diaphragm muscle was removed and separated into two blocks for Pax7 mRNA and protein measurement. Total RNA was extracted from one block and the level of Pax7 mRNA expression was determined using RT-PCR. To determine the location of Pax7 protein and number of satellite cells in each muscle fiber type, 10-µm serial sections were cut from another block using a freezing-microtome, and then immunohistochemical procedures were performed on these sections with antibodies to laminin, Pax7, myosin heavy chain (Fast or IIa) and DAPI. RESULTS: In the young group, the level of Pax7 mRNA expression was five-fold higher in the CAC group than in the CTL group. However, there was no change in the level of Pax7 mRNA expression in the old group. There were no significant changes in either composition or muscle fiber areas caused by CAC in either age group. There were no significant changes in the numbers of satellite cells of type I or IIa fibers in either age group. However, in type IIx/b fiber, the number of satellite cells was significantly higher in the CAC group (0.23±0.16) than in the CTL (0.08±0.04) group in young animals, but not in old animals. CONCLUSIONS: In a previous study, we confirmed a 40% increase in activity (iEMG) due to CAC in the rat hemi-diaphragm. Our findings indicate that satellite cell activation may be induced by extreme activation of muscle fiber without causing muscle fiber hypertrophy in young muscles. However, neither Pax7 mRNA nor satellite cells numbers was increased in the activated aged muscle. Therefore, we concluded that the potential for activation in satellite cells themselves is impaired due to aging, resulting in functional disorder of muscle regenerative ability.

Activity of bilateral posterior cricoarytenoid muscle satellite cell after denervation or reinnervation with ansa in dogs

To investigate the activity of bilateral posterior cricoarytenoid muscle satellite cell after denervation or reinnervation with ansa cervicalis. Twenty four dogs were randomly divided into 3 groups. The bilateral laryngeal recurrent nerves were cut in group one in all dogs. The bilateral laryngeal recurrent nerves were anastomosed with ansa cervicalis after incision in group two in all dogs. The dogs in group three were used as control. Nine weeks after surgery, the electromyography was used to test the regeneration of the nerve. The posterior cricoarytenoid muscles biopsy were collected. The expression of mRNA of Myogenin, Myf5, and Pax7 was assayed by realtime RT-PCR after total RNA isolation. Two dogs died after surgery in incision and anastomose group. The electromyography suggested that the RLN of all dogs had denervated in the incision group and had reinnervated in the anastomose group after 9 weeks. Myogenin mRNA from RLN incision dogs PCA muscles had greater expression versus controls (Z = 1.42, P < 0.01) or anastomosed dogs (Z = 1.38, P < 0.01). Myf5 mRNA expression from RLN incision dogs PCA muscles had significant increase versus control dogs (Z = 1.66, P < 0.01) or anastomosed dogs (Z = 1.69, P < 0.01). Pax7 mRNA expression from RNL incision dogs had significant increase compared with control (Z = 1.66, P < 0.01) or anastomosed animals (Z = 1.42, P < 0.05). There was no significant difference in Myogenin (Z = 1.34, P > 0.05), Myf5 (Z = 0.54, P > 0.05) and Pax (Z = 0.54, P > 0.05) mRNA expression between controls and anastomosed animals. The bilateral denervation of RLN cause significantly increasing in dog PCA muscle satellite cell proliferation and differentiation. The bilateral reinnervation of RLN cause PCA muscle satellite cell come back nonproliferative, quiescent state in dog.

Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis

A common characteristic of aging is loss of skeletal muscle (sarcopenia), which can lead to falls and fractures. MicroRNAs (miRNAs) are novel posttranscriptional modulators of gene expression with potential roles as regulators of skeletal muscle mass and function. The purpose of this study was to profile miRNA expression patterns in aging human skeletal muscle with a miRNA array followed by in-depth functional and network analysis. Muscle biopsy samples from 36 men [young: 31 ± 2 (n = 19); older: 73 ± 3 (n = 17)] were 1) analyzed for expression of miRNAs with a miRNA array, 2) validated with TaqMan quantitative real-time PCR assays, and 3) identified (and later validated) for potential gene targets with the bioinformatics knowledge base software Ingenuity Pathways Analysis. Eighteen miRNAs were differentially expressed in older humans (P < 0.05 and >500 expression level). Let-7 family members Let-7b and Let-7e were significantly elevated and further validated in older subjects (P < 0.05). Functional and network analysis from Ingenuity determined that gene targets of the Let-7s were associated with molecular networks involved in cell cycle control such as cellular proliferation and differentiation. We confirmed with real-time PCR that mRNA expression of cell cycle regulators CDK6, CDC25A, and CDC34 were downregulated in older compared with young subjects (P < 0.05). In addition, PAX7 mRNA expression was lower in older subjects (P < 0.05). These data suggest that aging is characterized by a higher expression of Let-7 family members that may downregulate genes related to cellular proliferation. We propose that higher Let-7 expression may be an indicator of impaired cell cycle function possibly contributing to reduced muscle cell renewal and regeneration in older human muscle.

Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men

BackgroundWe aimed to determine the effect of resistance exercise intensity (% 1 repetition maximum—1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.Methodology/Principal FindingsFifteen men (21±1 years; BMI = 24.1±0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P = 0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P = 0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P = 0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.Conclusions/SignificanceThese results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.