Adaptive Response Of Skeletal Muscle Research Articles

Adaptive responses of skeletal muscle to calcaneal tendon partial injury in rats: insights into remodeling and plasticity.

Skeletal muscle is a highly adaptive tissue, capable of responding to different physiological and functional demands, even in situations that may cause instability. To evaluate how partial calcaneal tendon (CT) injuries affect the remodeling and plasticity of the gastrocnemius muscle over time. The study was carried out with Wistar rats randomly divided into five groups. The control group comprised animals not subjected to partial CT damage. The remaining four groups were subjected to partial CT damage and were further categorized based on the time of euthanasia: 3, 14, 28, and 55 days after injury. The gastrocnemius muscle was collected and used for gene expression analysis, zymography, flow cytometry, and morphology. The calcaneal tendon was analyzed only to verify the presence of the partial injury. The impact of partial CT injury on the gastrocnemius homeostasis, particularly on gene expression, was more pronounced in the 3-day group compared to the other groups, especially the control group. Cytokine profile and morphologic alterations occurred in the 55 days group when compared to the other groups. The data reported here suggest that partial injury can negatively affect intracellular signaling and degradation pathways, disturbing the muscular extracellular matrix regulatory mechanisms and communication with the tendon. However, skeletal muscle seems to mitigate these harmful effects in comparison with lesions that affect muscle and tendon.

Repeated passive heat treatment increases muscle tissue capillarization, but does not affect postprandial muscle protein synthesis rates in healthy older adults.

Prolonged passive heat treatment (PHT) has been suggested to trigger skeletal muscle adaptations that may improve muscle maintenance in older individuals. To assess the effects of PHT on skeletal muscle tissue capillarization, perfusion capacity, protein synthesis rates, hypertrophy and leg strength, 14 older adults (9males, 5 females; 73 ± 6years) underwent 8weeks of PHT (infrared sauna: 3× per week, 45min at ∼60°C). Before and after PHT we collected muscle biopsies to assess skeletal muscle capillarization and fibre cross-sectional area (CSA). Basal and postprandial muscle tissue perfusion kinetics and protein synthesis rates were assessed using contrast-enhanced ultrasound and primed continuous l-[ring-13C6]phenylalanine infusions, respectively. One-repetition maximum (1RM) leg strength and vastus lateralis muscle CSA were assessed. Type I and type II muscle fibre capillarization strongly increased following PHT (capillary-to-fibre perimeter exchange index: +31 ± 18 and +33 ± 30%, respectively; P<0.001). No changes were observed in basal (0.24 ± 0.27 vs. 0.18 ± 0.11 AU; P=0.266) or postprandial (0.20 ± 0.12 vs. 0.18 ± 0.14 AU; P=0.717) microvascular blood flow following PHT. Basal (0.048 ± 0.014 vs. 0.051 ± 0.019%/h; P=0.630) and postprandial (0.041 ± 0.012 vs. 0.051 ± 0.024%/h; P=0.199) muscle protein synthesis rates did not change in response to prolonged PHT. Furthermore, no changes in vastus lateralis muscle CSA (15.3 ± 4.6 vs. 15.2 ± 4.6 cm2; P=0.768) or 1RM leg strength (46 ± 12 vs. 47 ± 12 kg; P=0.087) were observed over time. In conclusion, prolonged PHT increases muscle tissue capillarization but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates in healthy, older adults. Prolonged PHT does not induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults. KEY POINTS: Repeated exposure to heat has been suggested to trigger skeletal muscle adaptive responses. We investigated the effect of 8weeks of whole-body passive heat treatment (PHT; infrared sauna: 3× per week for 45min at ∼60°C) on skeletal muscle tissue capillarization, perfusion capacity, basal, and postprandial muscle protein synthesis rates, muscle (fibre) hypertrophy, and leg strength in healthy, older adults. Prolonged PHT increases muscle tissue capillarization, but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates. Despite increases in muscle tissue capillarization, prolonged PHT does not suffice to induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults.

Methylglyoxal reduces resistance exercise-induced protein synthesis and anabolic signaling in rat tibialis anterior muscle.

Resistance exercise provides significant benefits to skeletal muscle, including hypertrophy and metabolic enhancements, supporting overall health and disease management. However, skeletal muscle responsiveness to resistance exercise is significantly reduced in conditions such as aging and diabetes. Recent reports suggest that glycation stress contributes to muscle atrophy and impaired exercise-induced muscle adaptation; however, its role in the muscle response to resistance exercise remains unclear. Therefore, in this study, we investigated whether methylglyoxal (MGO), a key factor in glycation stress, affects the acute responsiveness of skeletal muscles to resistance exercise, focusing on protein synthesis and the key signaling molecules. This study included 12 8-week-old male Sprague-Dawley rats divided into two groups: one received 0.5% MGO-supplemented drinking water (MGO group) and the other received regular water (control group). After 10 weeks, the left tibialis anterior muscle of each rat was subjected to electrical stimulation (ES) to mimic resistance exercise, with the right muscle serving as a non-stimulated control. Muscle protein-synthesis rates were evaluated with SUnSET, and phosphorylation levels of key signaling molecules (p70S6K and S6rp) were quantified using western blotting. In the control group, stimulated muscles exhibited significantly increased muscle protein synthesis and phosphorylation levels of p70S6K and S6rp. In the MGO group, these increases were attenuated, indicating that MGO treatment suppresses the adaptive response to resistance exercise. MGO diminishes the skeletal muscle's adaptive response to ES-simulated resistance exercise, affecting both muscle protein synthesis and key signaling molecules. The potential influence of glycation stress on the effectiveness of resistance exercise or ES emphasizes the need for individualized interventions in conditions of elevated glycation stress, such as diabetes and aging.

Exercise microdosing for skeletal muscle health applications to spaceflight.

Findings from a recent 70-day bedrest investigation suggested intermittent exercise testing in the control group may have served as a partial countermeasure for skeletal muscle size, function, and fiber-type shifts. The purpose of the current study was to investigate the metabolic and skeletal muscle molecular responses to the testing protocols. Eight males (29 ± 2 yr) completed muscle power (6 × 4 s; peak muscle power: 1,369 ± 86 W) and V̇o2max (13 ± 1 min; 3.2 ± 0.2 L/min) tests on specially designed supine cycle ergometers during two separate trials. Blood catecholamines and lactate were measured pre-, immediately post-, and 4-h postexercise. Muscle homogenate and muscle fiber-type-specific [myosin heavy chain (MHC) I and MHC IIa] mRNA levels of exercise markers (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4) and MHC I, IIa, and IIx were measured from vastus lateralis muscle biopsies obtained pre- and 4-h postexercise. The muscle power test altered (P ≤ 0.05) norepinephrine (+124%), epinephrine (+145%), lactate (+300%), and muscle homogenate mRNA (IκBα, myogenin, MuRF-1, RRAD, Fn14). The V̇o2max test altered (P ≤ 0.05) norepinephrine (+1,394%), epinephrine (+1,412%), lactate (+736%), and muscle homogenate mRNA (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4). In general, both tests influenced MHC IIa muscle fibers more than MHC I with respect to the number of genes that responded and the magnitude of response. Both tests also influenced MHC mRNA expression in a muscle fiber-type-specific manner. These findings provide unique insights into the adaptive response of skeletal muscle to small doses of exercise and could help shape exercise dosing for astronauts and Earth-based individuals.NEW & NOTEWORTHY Declines in skeletal muscle health are a concern for astronauts on long-duration spaceflights. The current findings add to the growing body of exercise countermeasures data, suggesting that small doses of specific exercise can be beneficial for certain aspects of skeletal muscle health. This information can be used in conjunction with other components of existing exercise programs for astronauts and might translate to other areas focused on skeletal muscle health (e.g., sports medicine, rehabilitation, aging).

Inhibition of p53-MDM2 binding reduces senescent cell abundance and improves the adaptive responses of skeletal muscle from aged mice.

Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice. The goal of this study was to determine if a novel pharmaceutical agent (BI01), which functions by upregulating p53 through inhibition of binding to MDM2, the primary p53 regulatory protein, improves muscle regeneration and hypertrophy in old mice. BI01 effectively reduced the number of senescent cells in vitro but had no effect on MPC survival or proliferation at a comparable dose. Following repeated oral gavage with 2mg/kg of BI01 (OS) or vehicle (OV), old mice (24months) underwent unilateral BaCl2 injury in the tibialis anterior (TA) muscle, with PBS injections serving as controls. After 7days, satellite cell number was higher in the TA of OS compared to OV mice, as was the expression of genes involved in ATP production. By 35days, old mice treated with BI01 displayed reduced senescent cell burden, enhanced regeneration (higher muscle mass and fiber cross-sectional area) and restoration of muscle function relative to OV mice. To examine the impact of 2mg/kg BI01 on muscle hypertrophy, the plantaris muscle was subjected to 28days of mechanical overload (MOV) in OS and OV mice. In response to MOV, OS mice had larger plantaris muscles and muscle fibers than OV mice, particularly type 2b + x fibers, associated with reduced senescent cells. Together our data show that BI01 is an effective senolytic agent that may also augment muscle metabolism to enhance muscle regeneration and hypertrophy in old mice.

Methylome and proteome integration in human skeletal muscle uncover group and individual responses to high-intensity interval training.

Exercise is a major beneficial contributor to muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple molecular layers (i.e., epigenome, transcriptome, and proteome). Identifying robust, across-molecular level targets associated with exercise response, at both group and individual levels, is paramount to develop health guidelines and targeted health interventions. Sixteen, apparently healthy, moderately trained (VO2 max = 51.0 ± 10.6 mL min-1 kg-1 ) males (age range = 18-45 years) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a longitudinal study composed of 12-week high-intensity interval training (HIIT) intervention. Vastus lateralis muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. DNA methylation (~850 CpG sites) and proteomic (~3000 proteins) analyses were conducted at all time points. Mixed models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. A total of 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst methylome overall shifted with training only one differentially methylated position (DMP) was significant (adj.p-value < .05). K-means analysis revealed cumulative protein changes by clusters of proteins that presented similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had large effect-sizes >0.5, among them are two novel exercise-related proteins, LYRM7 and EPN1. Integration analysis showed bidirectional relationships between the methylome and proteome. We showed a significant influence of HIIT on the epigenome and more so on the proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of these proteins in response to exercise.

The exercise-mediated metabokine Beta-aminoisobutyric acid is an exercise mimetic driving skeletal muscle metabolic and functional adaptation

Skeletal muscle integrates many of the systemic signals, which contribute to the adaptive remodeling, and beneficial effects of exercise. One mechanism through which muscle mediates the systemic effects of exercise is through muscle-derived hormones known as myokines. We identified the metabolite β-aminoisobutyric acid (BAIBA) as an exercise-mediated small molecule myokine. BAIBA is secreted from muscle in response to increased expression of the transcriptional co-regulator PGC-1α, a master regulator of the muscle adaptive response to exercise. However, how BAIBA functions to regulate the adaptive responses of skeletal muscle to exercise remains poorly understood. We show that BAIBA improves muscle metabolism, exercise efficiency and performance in mice. Oxygen consumption (VO2) and energy expenditure are increased in BAIBA-treated mice. Furthermore, BAIBA increased soleus in situ muscle contractile force, fatigue resistance, mitochondrial number and function. We found that BAIBA drives muscle fiber-type switching to an oxidative phenotype in vivo. BAIBA regulates specific fiber-type gene expression in human myocytes through PPARΔ. Our findings demonstrate that BAIBA is a key paracrine myokine, which, in part, regulates the effects of exercise to improve muscle function with resultant effects on exercise performance. H.N.D. acknowledges the support of the Biotechnology and Biological Sciences Research Council (BB/T004231/1). This is the full abstract presented at the American Physiology Summit 2023 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.

Mass spectrometry-based proteomics approaches to interrogate skeletal muscle adaptations to exercise.

Acute exercise and chronic exercise training elicit beneficial whole-body changes in physiology that ultimately depend on profound alterations to the dynamics of tissue-specific proteins. Since the work accomplished during exercise owes predominantly to skeletal muscle, it has received the majority of interest from exercise scientists that attempt to unravel adaptive mechanisms accounting for salutary metabolic effects and performance improvements that arise from training. Contemporary scientists are also beginning to use mass spectrometry-based proteomics, which is emerging as a powerful approach to interrogate the muscle protein signature in a more comprehensive manner. Collectively, these technologies facilitate the analysis of skeletal muscle protein dynamics from several viewpoints, including changes to intracellular proteins (expression proteomics), secreted proteins (secretomics), post-translational modifications as well as fiber-, cell-, and organelle-specific changes. This review aims to highlight recent literature that has leveraged new workflows and advances in mass spectrometry-based proteomics to further our understanding of training-related changes in skeletal muscle. We call attention to untapped areas in skeletal muscle proteomics research relating to exercise training and metabolism, as well as basic points of contention when applying mass spectrometry-based analyses, particularly in the study of human biology. We further encourage researchers to couple the hypothesis-generating and descriptive nature of omics data with functional analyses that propel our understanding of the complex adaptive responses in skeletal muscle that occur with acute and chronic exercise.

Vegan and Omnivorous High Protein Diets Support Comparable Daily Myofibrillar Protein Synthesis Rates and Skeletal Muscle Hypertrophy in Young Adults

BackgroundIt remains unclear whether non–animal-derived dietary protein sources (and therefore vegan diets) can support resistance training-induced skeletal muscle remodeling to the same extent as animal-derived protein sources. MethodsIn Phase 1, 16 healthy young adults (m = 8, f = 8; age: 23 ± 1 y; BMI: 23 ± 1 kg/m2) completed a 3-d dietary intervention (high protein, 1.8 g·kg bm−1·d−1) where protein was derived from omnivorous (OMNI1; n = 8) or exclusively non-animal (VEG1; n = 8) sources, alongside daily unilateral leg resistance exercise. Resting and exercised daily myofibrillar protein synthesis (MyoPS) rates were assessed using deuterium oxide. In Phase 2, 22 healthy young adults (m = 11, f = 11; age: 24 ± 1 y; BMI: 23 ± 0 kg/m2) completed a 10 wk, high-volume (5 d/wk), progressive resistance exercise program while consuming an omnivorous (OMNI2; n = 12) or non–animal-derived (VEG2; n = 10) high-protein diet (∼2 g·kg bm−1·d−1). Muscle fiber cross-sectional area (CSA), whole-body lean mass (via DXA), thigh muscle volume (via MRI), muscle strength, and muscle function were determined pre, after 2 and 5 wk, and postintervention. ObjectivesTo investigate whether a high-protein, mycoprotein-rich, non-animal-derived diet can support resistance training-induced skeletal muscle remodeling to the same extent as an isonitrogenous omnivorous diet. ResultsDaily MyoPS rates were ∼12% higher in the exercised than in the rested leg (2.46 ± 0.27%·d−1 compared with 2.20 ± 0.33%·d−1 and 2.62 ± 0.56%·d−1 compared with 2.36 ± 0.53%·d−1 in OMNI1 and VEG1, respectively; P < 0.001) and not different between groups (P > 0.05). Resistance training increased lean mass in both groups by a similar magnitude (OMNI2 2.6 ± 1.1 kg, VEG2 3.1 ± 2.5 kg; P > 0.05). Likewise, training comparably increased thigh muscle volume (OMNI2 8.3 ± 3.6%, VEG2 8.3 ± 4.1%; P > 0.05), and muscle fiber CSA (OMNI2 33 ± 24%, VEG2 32 ± 48%; P > 0.05). Both groups increased strength (1 repetition maximum) of multiple muscle groups, to comparable degrees. ConclusionsOmnivorous and vegan diets can support comparable rested and exercised daily MyoPS rates in healthy young adults consuming a high-protein diet. This translates to similar skeletal muscle adaptive responses during prolonged high-volume resistance training, irrespective of dietary protein provenance.This trial was registered at clinicaltrials.gov as NCT03572127.

Raw Eggs To Support Postexercise Recovery in Healthy Young Men: Did Rocky Get It Right or Wrong?

Egg protein is ingested during recovery from exercise to facilitate the postexercise increase in muscle protein synthesis rates and, as such, to support the skeletal muscle adaptive response to exercise training. The impact of cooking egg protein on postexercise muscle protein synthesis is unknown. We sought to compare the impact of ingesting unboiled (raw) compared with boiled eggs during postexercise recovery on postprandial myofibrillar protein synthesis rates. In a parallel design, 45 healthy, resistance-trained young men (age: 24 y; 95% CI: 23, 25 y) were randomly assigned to ingest 5 raw eggs (∼30 g protein), 5 boiled eggs (∼30 g protein), or a control breakfast (∼5 g protein) during recovery from a single session of whole-body resistance-type exercise. Primed continuous l-[ring-13C6]-phenylalanine infusions were applied, with frequent blood sampling. Muscle biopsies were collected immediately after cessation of resistance exercise and at 2 and 5 h into the postexercise recovery period. Primary (myofibrillar protein synthesis rates) and secondary (plasma amino acid concentrations) outcomes were analyzed using repeated-measures (time × group) ANOVA. Ingestion of eggs significantly increased plasma essential amino acid (EAA) concentrations, with 20% higher peak concentrations following ingestion of boiled compared with raw eggs (time × group: P < 0.001). Myofibrillar protein synthesis rates were significantly increased during the postexercise period when compared with basal, postabsorptive values in all groups (2-4-fold increase: P < 0.001). Postprandial myofibrillar protein synthesis rates were 20% higher after ingesting raw eggs [0.067%/h; 95% CI: 0.056, 0.077%/h; effect size (Cohen d): 0.63], and 18% higher after ingesting boiled eggs (0.065%/h; 95% CI: 0.058, 0.073%/h; effect size: 0.69) when compared with the control breakfast (0.056%/h; 95% CI: 0.048, 0.063%/h), with no significant differences between groups (time × group: P = 0.077). The ingestion of raw, as opposed to boiled, eggs attenuates the postprandial rise in circulating EAA concentrations. However, postexercise muscle protein synthesis rates do not differ after ingestion of 5 raw compared with 5 boiled eggs in healthy young men. This trial was registered at the Nederlands Trial Register as NL6506 (www.trialregister.nl).

Aerobic conditioning alters the satellite cell and ribosome response to acute eccentric contractions in young men and women.

Satellite cells (SCs) and ribosomes are key determinants of the skeletal muscle adaptive response. Both are thought to increase acutely after resistance exercise and chronically with resistance training. However, the acute SC and ribosome exercise response with prior aerobic conditioning is unknown. Fourteen young men and women underwent 6 wk of single-legged aerobic conditioning followed by an acute bout of 300 eccentric contractions on each leg. Muscle biopsies were taken from the vastus lateralis of the aerobically conditioned (AC) and the control (CTL) legs before (Pre), 24 (24 h), and 48 (48 h) h post-contractions. Pre-eccentric contractions, 45S pre-rRNA and 5.8S internal transcribed spacer (ITS) expression were lower in the AC leg compared with the CTL leg. SC content (PAX7+ cells/100 fibers) in type I and mixed fibers showed a main effect of condition, where values were greater in the AC leg compared with the CTL. A main effect of condition for Pax7 and MyoD1 mRNA expression was observed where expression was greater in the AC leg compared with the CTL. AC had greater RNA concentration and mRNA expression of Ubf and Tif-1a compared with CTL. Only the AC leg increased (Pre-24h) 45S pre-rRNA, 5.8S ITS, and 28S ITS following eccentric contractions. We discovered that aerobic conditioning increased type-I SC abundance and the acute increase in ribosome content following eccentric contractions.

Myokine Response to Resistance Exercise in Older Adults and the Similarities and Differences to Younger Adults: A Brief Narrative Review

Myokines are cytokines secreted from muscle during contraction and are implicated in autocrine, paracrine, and endocrine regulation of biological systems. It is postulated that myokines contribute to skeletal muscle adaptations in response to resistance exercise. Exercise, including resistance exercise, is an important factor in the management of maintaining skeletal muscle strength, mass, and function with aging. Sarcopenia is exacerbated with increased age and therefore, it is important to understand the potential underlying mechanisms whereby exercise may be beneficial in reducing the consequences of sarcopenia for older adults. Myokine secretion is one mechanism which is postulated to account for the benefits of exercise in aging muscle. The response of myokines to aerobic exercise in older adults have previously been reviewed; however, there is limited research focused on the response of myokines to resistance exercise. Therefore, the aim of this narrative review is to discuss the response of various myokines to an acute bout of resistance exercise and/or chronic resistance exercise training in older adults, compare the response between younger and older adults, and briefly outline the influence myokines may have on skeletal muscle adaptations.

Role of autophagy in the maintenance of skeletal muscle mass

As an important exercise and energy metabolism organ of the human body, the normal maintenance of skeletal muscle mass is essential for the body to perform normal physiological functions. The autophagy-lysosome (AL) pathway is a physiological or pathological mechanism that is ubiquitous in normal and diseased cells. It plays a key role in the maintaining of protein balance, removing damaged organelles, and the stability of internal environment. The smooth progress of the autophagy process needs to go through multiple steps, which are completed under the coordinated action of multiple factors. Autophagy maintains the muscle homeostasis of a healthy body by removing cell components such as damaged myofibrils and isolated cytoplasmic proteins. Autophagy could also provide the initial energy required for cell proliferation, promote muscle regeneration and remodeling after injury. At the same time, autophagy disorder is also an important cause of age-related skeletal muscle atrophy. Autophagy could affect the response of skeletal muscle to exercise, and increasing the level of basic autophagy is beneficial to improve the adaptive response of skeletal muscle to exercise. This article summarizes the role and pathways of autophagy in the maintenance of skeletal muscle quality, in order to provide effective rehabilitation strategies for clinical prevention and treatment of muscle atrophy.

Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies.

BackgroundExercise elicits a range of adaptive responses in skeletal muscle, which include changes in mRNA expression. To better understand the health benefits of exercise training, it is important to investigate the underlying molecular mechanisms of skeletal muscle adaptation to exercise. However, most studies have assessed the molecular events at only a few time-points within a short time frame post-exercise, and the variations of gene expression kinetics have not been addressed systematically.MethodsWe assessed the mRNA expression of 23 gene isoforms implicated in the adaptive response to exercise at six time-points (0, 3, 9, 24, 48, and 72 h post exercise) over a 3-day period following a single session of high-intensity interval exercise.ResultsThe temporal patterns of target gene expression were highly variable and the expression of mRNA transcripts detected was largely dependent on the timing of muscle sampling. The largest fold change in mRNA expression of each tested target gene was observed between 3 and 72 h post-exercise.Discussion and ConclusionsOur findings highlight an important gap in knowledge regarding the molecular response to exercise, where the use of limited time-points within a short period post-exercise has led to an incomplete understanding of the molecular response to exercise. Muscle sampling timing for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.

Early resistance training-mediated stimulation of daily muscle protein synthetic responses to higher habitual protein intake in middle-aged adults.

The ingestion of protein potentiates the stimulation of myofibrillar protein synthesis rates after an acute bout of resistance exercise. Protein supplementation (eating above the protein Recommended Dietary Allowance) during resistance training has been shown to maximize lean mass and strength gains in healthy young and older adults. Here, contractile, oxidative, and structural protein synthesis were assessed in skeletal muscle in response to a moderate or higher protein diet during the early adaptive phase of resistance training in middle-aged adults. The stimulation of myofibrillar, mitochondrial or collagen protein synthesis rates during 0-3weeks of resistance training is not further enhanced by a higher protein diet. These results show that moderate protein diets are sufficient to support the skeletal muscle adaptive response during the early phase of a resistance training programme. Protein ingestion augments muscle protein synthesis (MPS) rates acutely after resistance exercise and can offset age-related loss in muscle mass. Skeletal muscle contains a variety of protein pools, such as myofibrillar (contractile), mitochondrial (substrate oxidation), and collagen (structural support) proteins, and the sensitivity to nutrition and exercise seems to be dependent on the major protein fraction studied. However, it is unknown how free-living conditions with high dietary protein density and habitual resistance exercise mediates muscle protein subfraction synthesis. Therefore, we investigated the effect of moderate (MOD: 1.06±0.22gkg-1 day-1 ) or high (HIGH: 1.55±0.25gkg-1 day-1 ) protein intake on daily MPS rates within the myofibrillar (MyoPS), mitochondrial (MitoPS) and collagen (CPS) protein fractions in middle-aged men and women (n=20, 47±1years, BMI 28±1kgm-2 ) during the early phase (0-3weeks) of a dietary counselling-controlled resistance training programme. Participants were loaded with deuterated water, followed by daily maintenance doses throughout the intervention. Muscle biopsies were collected at baseline and after weeks 1, 2 and 3. MyoPS in the HIGH condition remained constant (P=1.000), but MOD decreased over time (P=0.023). MitoPS decreased after 0-3weeks when compared to 0-1week (P=0.010) with no effects of protein intake (P=0.827). A similar decline with no difference between groups (P=0.323) was also observed for CPS (P=0.007). Our results demonstrated that additional protein intake above moderate amounts does not potentiate the stimulation of longer-term MPS responses during the early stage of resistance training adaptations in middle-aged adults.

PGC-1α regulates myonuclear accretion after moderate endurance training.

The transcriptional demands of skeletal muscle fibres are high and require hundreds of nuclei (myonuclei) to produce specialised contractile machinery and multiple mitochondria along their length. Each myonucleus spatially regulates gene expression in a finite volume of cytoplasm, termed the myonuclear domain (MND), which positively correlates with fibre cross-sectional area (CSA). Endurance training triggers adaptive responses in skeletal muscle, including myonuclear accretion, decreased MND sizesand increased expression of the transcription co-activator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Previous work has shown that overexpression of PGC-1α in skeletal muscle regulates mitochondrial biogenesis, myonuclear accretion and MND volume. However, whether PGC-1α is critical for these processes in adaptation to endurance training remained unclear. To test this, we evaluated myonuclear distribution and organisation in endurance-trained wild-type mice and mice lacking PGC-1α in skeletal muscle (PGC-1α mKO). Here, we show a differential myonuclear accretion response to endurance training that is governed by PGC-1α and is dependent on muscle fibre size. The positive relationship of MND size and muscle fibre CSA trended towards a stronger correlation in PGC-1a mKO versus control after endurance training, suggesting that myonuclear accretion was slightly affected with increasing fibre CSA in PGC-1α mKO. However, in larger fibres, the relationship between MND and CSA was significantly altered in trained versus sedentary PGC-1α mKO, suggesting that PGC-1α is critical for myonuclear accretion in these fibres. Accordingly, there was a negative correlation between the nuclear number and CSA, suggesting that in larger fibres myonuclear numbers fail to scale with CSA. Our findings suggest that PGC-1α is an important contributor to myonuclear accretion following moderate-intensity endurance training. This may contribute to the adaptive response to endurance training by enabling a sufficient rate of transcription of genes required for mitochondrial biogenesis.

Skeletal Muscle Adaptive Responses to Different Types of Short-Term Exercise Training and Detraining in Middle-Age Men.

Whether short-term, single-mode exercise training can improve physical fitness before a period of reduced physical activity (e.g., postsurgery recovery) is not well characterized in clinical populations or middle-age adults. We investigated skeletal muscle adaptive responses after endurance exercise training (ENT), high-intensity interval training (HIIT), or resistance exercise training (RET), and a subsequent period of detraining, in sedentary, middle-age men. Thirty-five sedentary men (39 ± 3 yr) were randomized to parallel groups and undertook 6 wk of either ENT (n = 12), HIIT (n = 12), or RET (n = 11) followed by 2.5 wk of detraining. Skeletal muscle fiber characteristics, body composition, muscle thickness, muscle strength, aerobic capacity, resting energy expenditure, and glucose homeostasis were assessed at baseline, and after exercise training and detraining. Lean mass increased after RET and HIIT (+3.2% ± 1.6% and +1.6% ± 2.1%, P < 0.05). Muscle strength (sum of leg press, leg extension, and bench press one-repetition maximums) increased after all training interventions (RET, +25% ± 5%; HIIT, +10% ± 5%; ENT, +7% ± 7%; P < 0.05). Aerobic capacity increased only after HIIT and ENT (+14% ± 7% and +11% ± 11%, P < 0.05). Type I and II muscle fiber size increased for all groups after training (main effect of time, P < 0.05). After a period of detraining, the gains in lean mass and maximal muscle strength were maintained in the RET and HIIT groups, but maximal aerobic capacity declined below posttraining levels in HIIT and ENT (P < 0.05). Six weeks of HIIT induced widespread adaptations before detraining in middle-age men. Exercise training-induced increases in aerobic capacity declined during 2.5 wk of detraining, but gains in lean mass and muscle strength were maintained.

Insight into type 2 diabetes impaired exercising mitochondrial oxidative flux: is it blood flow, mitochondria, or neither?

Insight into type 2 diabetes impaired exercising mitochondrial oxidative flux: is it blood flow, mitochondria, or neither?

Blood flow restriction during the resting periods of high-intensity resistance training does not alter performance but decreases MIR-1 and MIR-133A levels in human skeletal muscle

Blood flow restriction (BFR) during exercise bouts has been used to induce hypertrophy of skeletal muscle, even with low loads. However, the effects of BFR during the rest periods between sets are not known. We have tested the hypothesis that BFR during rest periods between sets of high-intensity resistance training would enhance performance. Twenty-two young adult male university students were recruited for the current study, with n = 11 assigned to BFR and n = 11 to a control group. The results revealed that four weeks training at 70% of 1 RM, five sets and 10 repetitions, three times a week with and without BFR, resulted in similar progress in maximal strength and in the number of maximal repetitions. The miR-1 and miR-133a decreased significantly in the vastus lateralis muscle of BFR group compared to the group without BFR, while no significant differences in the levels of miR133b, miR206, miR486, and miR499 were found between groups. In conclusion, it seems that BFR restrictions during rest periods of high-intensity resistance training, do not provide benefit for enhanced performance after a four-week training program. However, BFR-induced downregulation of miR-1 and miR-133a might cause different adaptive responses of skeletal muscle to high intensity resistance training.

More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle

Skeletal muscle is a highly plastic tissue capable of remodeling in response to a range of physiological stimuli, including nutrients and exercise. Historically, the lysosome has been considered an essentially catabolic organelle contributing to autophagy, phagocytosis, and exo-/endocytosis in skeletal muscle. However, recent evidence has emerged of several anabolic roles for the lysosome, including the requirement for autophagy in skeletal muscle mass maintenance, the discovery of the lysosome as an intracellular signaling hub for mechanistic target of rapamycin complex 1 (mTORC1) activation, and the importance of transcription factor EB/lysosomal biogenesis-related signaling in the regulation of mTORC1-mediated protein synthesis. We, therefore, propose that the lysosome is an understudied organelle with the potential to underpin the skeletal muscle adaptive response to anabolic stimuli. Within this review, we describe the molecular regulation of lysosome biogenesis and detail the emerging anabolic roles of the lysosome in skeletal muscle with particular emphasis on how these roles may mediate adaptations to chronic resistance exercise. Furthermore, given the well-established role of amino acids to support muscle protein remodeling, we describe how dietary proteins "labeled" with stable isotopes could provide a complementary research tool to better understand how lysosomal biogenesis, autophagy regulation, and/or mTORC1-lysosomal repositioning can mediate the intracellular usage of dietary amino acids in response to anabolic stimuli. Finally, we provide avenues for future research with the aim of elucidating how the regulation of this important organelle could mediate skeletal muscle anabolism.