Relationship between intermuscular adipose tissue infiltration and myostatin before and after aerobic exercise training.

Intermuscular adipose tissue (IMAT) is associated with impaired skeletal muscle contractile and metabolic function. Myostatin and downstream signaling proteins such as cyclin-dependent kinase 2 (CDK2) contribute to the regulation of adipose and skeletal muscle mass in cell culture and animals models, but this relationship remains incompletely understood in humans. The purpose of this study was to determine if the infiltration of IMAT was associated with skeletal muscle myostatin and downstream proteins before and after 12 wk of aerobic exercise training (AET) in healthy older women (OW; 69 ± 2 yr), older men (OM; 74 ± 3 yr), and young men (YM; 20 ± 1 yr). We found that the infiltration of IMAT was correlated with myostatin and phosphorylated CDK2 at tyrosine 15 [P-CDK2(Tyr15)]. IMAT infiltration was greater in the older subjects and was associated with lower skeletal muscle function and exercise capacity. After 12 wk of AET, there was no change in body weight. Myostatin and P-CDK2(Tyr15) were both decreased after AET, and the reduction in myostatin was associated with decreased IMAT infiltration. The decrease in myostatin and IMAT occurred concomitantly with increased exercise capacity, skeletal muscle size, and function after AET. These findings demonstrate that the reduction in IMAT infiltration after AET in weight stable individuals was accompanied by improvements in skeletal muscle function and exercise capacity. Moreover, the association between myostatin and IMAT was present in the untrained state and in response to exercise training, strengthening the potential regulatory role of myostatin on IMAT.

Short-term intense exercise training reduces stress markers and alters the transcriptional response to exercise in skeletal muscle.

The purpose of this investigation was to examine the influence of short-term intense endurance training on cycling performance, along with the acute and chronic signaling responses of skeletal muscle stress and stability markers. Ten recreationally active subjects (25 ± 2 yr, 79 ± 3 kg, 47 ± 2 ml·kg-1·min-1) were studied before and after a 12-day cycling protocol to examine the effects of short-term intense (70-100% V̇o2max) exercise training on resting and exercise-induced regulation of molecular factors related to skeletal muscle cellular stress and protein stability. Skeletal muscle biopsies were taken at rest and 3 h following a 20-km cycle time trial on days 1 and 12 to measure mRNA expression and protein content. Training improved (P < 0.05) cycling performance by 5 ± 1%. Protein oxidation was unaltered on day 12, while resting SAPK/JNK phosphorylation was reduced (P < 0.05), suggesting a reduction in cellular stress. The maintenance in the myocellular environment may be due to synthesis of cytoprotective markers, along with enhanced degradation of damage proteins, as training tended (P < 0.10) to increase resting protein content of manganese superoxide dismutase and heat shock protein 70 (HSP70), while mRNA expression of MuRF-1 was elevated (P < 0.05). Following training (day 12), the acute exercise-induced transcriptional response of TNF-α, NF-κB, MuRF-1, and PGC1α was attenuated (P < 0.05) compared with day 1 Collectively, these data suggest that short-term intense training enhances protein stability, creating a cellular environment capable of resistance to exercise-induced stress, which may be favorable for adaptation.

Amino acid infusion alters the expression of growth-related genes in multiple skeletal muscles.

BACKGROUND: Exercise and nutritional interventions have been examined independently as countermeasures to offset the loss of skeletal muscle mass with unloading, yet a protocol to completely preserve the soleus has not been identified. Little is known regarding the combined effect of exercise and nutrition on factors regulating skeletal muscle growth. The purpose of this investigation was to evaluate the influence of amino acid (AA) infusion on myogenic (MRF-4, MyoD, and Myogenin), proteolytic (MuRF-1, Atrogin-1, FOXO3A, Calpain-1, Calpain-2, Caspase-3, Cathepsin L1), and cytokine (IL-6, IL-8, and IL-15) mRNA transcripts in two skeletal muscles that respond distinctly to microgravity unloading. METHODS: Muscle biopsies were obtained from the vastus lateralis (VL) and soleus of eight male subjects prior to and after 4 h of AA infusion for analysis of mRNA expression. All subjects performed a standardized exercise bout (45-min treadmill run) 24 h prior to the AA infusion. RESULTS: In the VL, proteolytic factors MuRF-1 and FOXO3A were reduced (44 +/- 9 and 28 +/- 6%, respectively) in response toAA infusion. In the soleus, mRNA transcripts of myogenic factor MRF-4 (91 +/- 36%) and cytokines IL-6, IL-8, and IL-15 were elevated while the proteolytic marker FOXO3A mRNA was reduced by 19 +/- 9%. DISCUSSION: These data suggest that the expression of genes related to skeletal muscle remodeling is altered during acute AA infusion 24 h post-exercise. It appears that increased amino acid availability in concert with exercise may create an intramuscular environment favorable for the prevention of muscle atrophy associated with unloading, which may be particularly beneficial for the soleus.

Increased cardiorespiratory fitness and skeletal muscle size following single-leg knee extension exercise training.

BACKGROUND: It is unclear to what extent an improved skeletal muscle phenotype influences maximal aerobic capacity (VO2max) when changes in cardiopulmonary function are limited. Thus, to primarily target skeletal muscle adaptations, we employed an alternating single-leg knee extension exercise training protocol and evaluated the impact on skeletal muscle morphology and whole-body exercise capacity. METHODS: Eight sedentary volunteers (20±1 years; VO2max: 38.4±2.6 mL/kg/min) completed 12 weeks of progressive alternating single-leg training. Subjects performed a bilateral maximal graded exercise test on a cycle ergometer, a single-leg peak workload test on a knee extensor ergometer, knee extension muscle function testing, and a dual energy X-ray absorptiometry scan before and after training. Skeletal muscle biopsies were obtained before and after the training protocol to assess muscle fiber type, by determining myosin heavy chain isoform composition using gel electrophoresis, and fiber size using immunofluorescent staining of muscle cross sections. RESULTS: Following training there were increases (P<0.05) in VO2max (2.53±0.25 vs. 2.76±0.20 L/min; 9±3%), the VO2 at ventilatory threshold (1.88±0.19 vs. 2.01±0.18 L/min; 8±2%), peak two-leg cycling workload (183±17 vs. 206±19 W; 13±2%), single-leg peak workload (40.0±4.4 vs. 55.3±5.1 W; 43±8%), skeletal muscle lean mass (3±1%), citrate synthase protein content (44±20%), as well as slow and fast myofiber size (13±4% and 14±4%, respectively) while there was a decrease (P<0.05) in hybrid fiber content (-33±8%). CONCLUSIONS: These data suggest that inducing a more oxidative phenotype in skeletal muscle with isolated aerobic exercise training improves cardiopulmonary responses to maximal exercise. Additionally, the low cardiovascular burden associated with isolated single-leg exercise may be a useful training approach for clinical populations with skeletal muscle dysfunction or cardiovascular limitations to exercise.

Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training.

Perturbations in mitochondrial health may foster age-related losses of aerobic capacity (VO2peak) and skeletal muscle size. However, limited data exist regarding mitochondrial dynamics in aging human skeletal muscle and the influence of exercise. The purpose of this study was to examine proteins regulating mitochondrial biogenesis and dynamics, VO2peak, and skeletal muscle size before and after aerobic exercise training in young men (20 ± 1 y) and older men (74 ± 3 y). Exercise-induced skeletal muscle hypertrophy occurred independent of age, whereas the improvement in VO2peak was more pronounced in young men. Aerobic exercise training increased proteins involved with mitochondrial biogenesis, fusion, and fission, independent of age. This is the first study to examine pathways of mitochondrial quality control in aging human skeletal muscle with aerobic exercise training. These data indicate normal aging does not influence proteins associated with mitochondrial health or the ability to respond to aerobic exercise training at the mitochondrial and skeletal muscle levels.