Skeletal muscle-specific expression of PGC-1α-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake

Background

Maximal oxygen uptake (VO_2max) predicts mortality and is associated with endurance performance. Trained subjects have a high VO_2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO_2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO_2max and exercise capacity.

Methodology/Principal Findings

Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.

Conclusions/Significance

Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise efficiently, which would lead to prevention of life-style related diseases and increased lifespan.     

Influence of exercise on the fiber composition of skeletal muscle

Summary Biopsy samples from the vastus lateralis muscle (VLM) of man were examined for fiber composition at rest and at selected intervals during prolonged exercise ranging in intensity from 40% to 75% of the total body maximal oxygen uptake (VO _2max) and one-min bouts of exercise at 150%VO _2max. Because of the heterogeneity of fibers in human VLM, studies were also completed where the effect of exercise on the fiber composition of the rat soleus muscle (SM) was examined. In some animals the SM from one hindlimb was removed 9 days prior to their being exercised after which the remaining SM was removed. Exercise reduced muscle glycogen in all experiments. In the studies with man, blood lactate exceeded 17 mmoles/l after the heavy exercise but was largely unchanged by endurance exercise. Colonic temperature of the exercised rats exceeded 40° C. In studies where fibers were identified only as type I and type II, type II fibers in the VLM of all samples (16) taken at rest averaged 61.2±12.5% as compared to 59.0±12.0% after exercise (54 biopsy samples). In a second series of studies with man where the subtypes of type II fibers were identified, there were also no differences in fiber composition of the VLM after varying periods of exercise. Glycogen content and percent fiber composition were the same in right and left SM obtained from rested rats. Exercise (30 to 40 min) did not alter the fiber composition of the rat SM. These data demonstrate that the histochemically demonstratable myofibrillar actomyosin ATPase of skeletal muscle is not altered by a single exercise bout.     

Short-Term Intensified Cycle Training Alters Acute and Chronic Responses of PGC1α and Cytochrome C Oxidase IV to Exercise in Human Skeletal Muscle

Reduced activation of exercise responsive signalling pathways have been reported in response to acute exercise after training; however little is known about the adaptive responses of the mitochondria. Accordingly, we investigated changes in mitochondrial gene expression and protein abundance in response to the same acute exercise before and after 10-d of intensive cycle training. Nine untrained, healthy participants (mean±SD; VO_2peak 44.1±17.6 ml/kg/min) performed a 60 min bout of cycling exercise at 164±18 W (72% of pre-training VO_2peak). Muscle biopsies were obtained from the vastus lateralis muscle at rest, immediately and 3 h after exercise. The participants then underwent 10-d of cycle training which included four high-intensity interval training sessions (6×5 min; 90–100% VO_2peak) and six prolonged moderate-intensity sessions (45–90 min; 75% VO_2peak). Participants repeated the pre-training exercise trial at the same absolute work load (64% of pre-training VO_2peak). Muscle PGC1-α mRNA expression was attenuated as it increased by 11- and 4- fold (P<0.001) after exercise pre- and post-training, respectively. PGC1-α protein expression increased 1.5 fold (P<0.05) in response to exercise pre-training with no further increases after the post-training exercise bout. RIP140 protein abundance was responsive to acute exercise only (P<0.01). COXIV mRNA (1.6 fold; P<0.01) and COXIV protein expression (1.5 fold; P<0.05) were increased by training but COXIV protein expression was decreased (20%; P<0.01) by acute exercise pre- and post-training. These findings demonstrate that short-term intensified training promotes increased mitochondrial gene expression and protein abundance. Furthermore, acute indicators of exercise-induced mitochondrial adaptation appear to be blunted in response to exercise at the same absolute intensity following short-term training.     

Acetic acid enhances endurance capacity of exercise-trained mice by increasing skeletal muscle oxidative properties

Acetic acid has been shown to promote glycogen replenishment in skeletal muscle during exercise training. In this study, we investigated the effects of acetic acid on endurance capacity and muscle oxidative metabolism in the exercise training using in vivo mice model. In exercised mice, acetic acid induced a significant increase in endurance capacity accompanying a reduction in visceral adipose depots. Serum levels of non-esterified fatty acid and urea nitrogen were significantly lower in acetic acid-fed mice in the exercised mice. Importantly, in the mice, acetic acid significantly increased the muscle expression of key enzymes involved in fatty acid oxidation and glycolytic-to-oxidative fiber-type transformation. Taken together, these findings suggest that acetic acid improves endurance exercise capacity by promoting muscle oxidative properties, in part through the AMPK-mediated fatty acid oxidation and provide an important basis for the application of acetic acid as a major component of novel ergogenic aids.     

Effect of ginger extract ingestion on skeletal muscle glycogen contents and endurance exercise in male rats

[Purpose]Skeletal muscle glycogen is a determinant of endurance capacity for some athletes. Ginger is well known to possess nutritional effects, such as anti-diabetic effects. We hypothesized that ginger extract (GE) ingestion increases skeletal muscle glycogen by enhancing fat oxidation. Thus, we investigated the effect of GE ingestion on exercise capacity, skeletal muscle glycogen, and certain blood metabolites in exercised rats. [Methods]First, we evaluated the influence of GE ingestion on body weight and elevation of exercise performance in rats fed with different volumes of GE. Next, we measured the skeletal muscle glycogen content and free fatty acid (FFA) levels in GE-fed rats. Finally, we demonstrated that GE ingestion contributes to endurance capacity during intermittent exercise to exhaustion. [Results]We confirmed that GE ingestion increased exercise performance (p<0.05) and elevated the skeletal muscle glycogen content compared to the non-GE-fed (CE, control exercise) group before exercise (Soleus: p<0.01, Plantaris: p<0.01, Gastrocnemius: p<0.05). Blood FFA levels in the GE group were significantly higher than those in the CE group after exercise (p<0.05). Moreover, we demonstrated that exercise capacity was maintained in the CE group during intermittent exercise (p<0.05). [Conclusion]These findings indicate that GE ingestion increases skeletal muscle glycogen content and exercise performance through the upregulation of fat oxidation.     

Exercise capacity of mice genetically lacking muscle glycogen synthase: in mice, muscle glycogen is not essential for exercise

The glucose storage polymer glycogen is generally considered to be an important source of energy for skeletal muscle contraction and a factor in exercise endurance. A genetically modified mouse model lacking muscle glycogen was used to examine whether the absence of the polysaccharide affects the ability of mice to run on a treadmill. The MGSKO mouse has the GYS1 gene, encoding the muscle isoform of glycogen synthase, disrupted so that skeletal muscle totally lacks glycogen. The morphology of the soleus and quadriceps muscles from MGSKO mice appeared normal. MGSKO-null mice, along with wild type littermates, were exercised to exhaustion. There were no significant differences in the work performed by MGSKO mice as compared with their wild type littermates. The amount of liver glycogen consumed during exercise was similar for MGSKO and wild type animals. Fasting reduced exercise endurance, and after overnight fasting, there was a trend to reduced exercise endurance for the MGSKO mice. These studies provide genetic evidence that in mice muscle glycogen is not essential for strenuous exercise and has relatively little effect on endurance.     

IL-6 and TNF-alpha expression in,and release from,contracting human skeletal muscle

The aim of the present study was to examine whether IL-6 and TNF-alpha are expressed in, and released from, human skeletal muscle during exercise. We hypothesized that the skeletal muscle will release IL-6, but not TNF-alpha, during exercise because of previous observations that TNF-alpha negatively affects glucose uptake in skeletal muscle. Six healthy, male subjects performed 180 min of two-legged knee-extensor exercise. Muscle samples were obtained from the vastus lateralis of one limb. In addition, blood samples were obtained from a femoral artery and vein. Plasma was analyzed for IL-6 and TNF-alpha. We detected both IL-6 and TNF-alpha mRNA in resting muscle samples, and whereas IL-6 increased (P < 0.05) approximately 100-fold throughout exercise, no significant increase in TNF-alpha mRNA was observed. Arterial plasma TNF-alpha did not increase during exercise. Furthermore, there was no net release of TNF-alpha either before or during exercise. In contrast, IL-6 increased throughout exercise in arterial plasma, and a net IL-6 release from the contracting limb was observed after 120 min of exercise (P < 0.05).     

Effects of one bout of endurance exercise on the expression of myogenin in human quadriceps muscle

The objective of this study was to investigate the cellular localisation of MyoD and myogenin in human skeletal muscle fibres as well as the possible alterations in the expression of MyoD and myogenin in response to a single bout of endurance exercise at 40% and 75% of maximum oxygen uptake (VO₂ max). Twenty-five biopsies (5 per subject) from the vastus lateralis muscle were obtained before exercise, from the exercising leg at 40% and 75% of VO₂ max and from the resting leg following these exercise bouts. The tyramide signal amplification-direct and the Vectastain ABC methods using specific monoclonal antibodies were used to determine the exact location of myogenin and MyoD, to identify muscle satellite cells and to determine myosin heavy chain (MyHC) composition. At rest, myonuclei did not express MyoD or myogenin. Following a single bout of exercise at 40% and 75% of VO₂ max, an accumulation of myogenin in myonuclei and not in satellite cells was observed in biopsies from the exercised leg but not in biopsies before exercise and from the resting leg. The number of myogenin-positive myonuclei varied among individuals indicating differences in the response to a single exercise bout. In conclusion, this immunohistochemical study showed that a rapid rearrangement of myogenin expression occurs in exercised human skeletal muscles in response to a single bout of exercise.     

Quadriceps and Respiratory Muscle Fatigue Following High-Intensity Cycling in COPD Patients

Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics, impaired O₂ transport and skeletal muscle dysfunction. However their relatie contribution and their influence on symptoms reported by patients remain to be clarified. In order to clarify the complex interaction between ventilatory and neuromuscular exercise limiting factors and symptoms, we evaluated respiratory muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms induced by exhaustive high-intensity cycling in COPD patients. Fifteen gold II-III COPD patients (age = 67±6 yr; BMI = 26.6±4.2 kg.m^-2) performed constant-load cycling test at 80% of their peak workload until exhaustion (9.3±2.4 min). Before exercise and at exhaustion, potentiated twitch quadriceps strength (Q_tw), transdiaphragmatic (P_di,tw) and gastric (P_ga,tw) pressures were evoked by femoral nerve, cervical and thoracic magnetic stimulation, respectively. Changes in operational lung volumes during exercise were assessed via repetitive inspiratory capacity (IC) measurements. Dyspnoea and leg discomfort were measured on visual analog scale. At exhaustion, Q_tw (-33±15%, >15% reduction observed in all patients but two) and P_di,tw (-20±15%, >15% reduction in 6 patients) were significantly reduced (P<0.05) but not P_ga,tw (-6±10%, >15% reduction in 3 patients). Percentage reduction in Q_tw correlated with the percentage reduction in P_di,tw (r=0.66; P<0.05). Percentage reductions in P_di,tw and P_ga,tw negatively correlated with the reduction in IC at exhaustion (r=-0.56 and r=-0.62, respectively; P<0.05). Neither dyspnea nor leg discomfort correlated with the amount of muscle fatigue. In conclusion, high-intensity exercise induces quadriceps, diaphragm and less frequently abdominal contractile fatigue in this group of COPD patients. In addition, the rise in end-expiratory lung volume and diaphragm flattening associated with dynamic hyperinflation in COPD might limit the development of abdominal and diaphragm muscle fatigue. This study underlines that both respiratory and quadriceps fatigue should be considered to understand the complex interplay of factors leading to exercise intolerance in COPD patients.     

Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men (n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher (P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold (P < 0.05) in response to exercise before the training period, but only 8-fold (P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 (P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.     

Vitamin D and Exercise Performance in Professional Soccer Players

Aim

The current study had two aims. The primary purpose was to examine the association between serum vitamin D levels and the ergometric evaluation of muscle strength, aerobic capacity, and speed in professional soccer players. The secondary aim was to evaluate the effects of the soccer off-season period on serum vitamin D levels.

Methods

Sixty-seven Caucasian male soccer players (age 25.6±6.2 and height 1.81±0.08 m), members of two Greek Superleague Soccer teams and one Football-league championship team participated in this study. Exercise performance testing for the determination of squat jump (SJ), countermovement jump (CMJ), 10 (10 m) and 20 meters (20 m) sprint performance, maximal oxygen consumption (VO₂max), anthropometry, and blood sampling were performed before (pre) and after (post) the six-week off-season period.

Results

Analysis of our results showed the following: (a) a significant correlations between serum vitamin D levels and performance parameters in both pre (SJ; P<0.001, CMJ; P<0.001, VO₂max; P<0.001, 10 m; P<0.001, and 20 m; P<0.001) and post (SJ; P<0.001, CMJ; P<0.001, VO₂max; P = 0.006, 10 m; P<0.001, and 20 m; P<0.001) experimental sessions. (b) Vitamin D concentration increased significantly (P<0.001) following the six-week off-season period compared to baseline, while at the same time all measured performance parameters decreased (SJ; P<0.001, CMJ; P<0.001, 10 m; P<0.001, 20 m; P<0.001, VO₂max; P<0.001).

Discussion

Our findings suggest that vitamin D levels are associated with the ergometric evaluation of muscle strength, as expressed by SJ and CMJ, sprinting capacity, and VO₂max in professional soccer players, irrespective the levels of performance. Furthermore, our data reaffirm the importance of UVB on serum vitamin D levels. Moreover, reductions in exercise training stress may also have beneficial effects on vitamin D levels, suggesting a possible association of its levels and the training-induced stress. Our results indicate a possibly bidirectional interaction between soccer performance indices and vitamin D levels.     

End Criteria for Reaching Maximal Oxygen Uptake Must Be Strict and Adjusted to Sex and Age: A Cross-Sectional Study

Objective

To describe different end criteria for reaching maximal oxygen uptake (VO_2max) during a continuous graded exercise test on the treadmill, and to explore the manner by which different end criteria have an impact on the magnitude of the VO_2max result.

Methods

A sample of 861 individuals (390 women) aged 20–85 years performed an exercise test on a treadmill until exhaustion. Gas exchange, heart rate, blood lactate concentration and Borg Scale_6–20 rating were measured, and the impact of different end criteria on VO_2max was studied;VO₂ leveling off, maximal heart rate (HR_max), different levels of respiratory exchange ratio (RER), and postexercise blood lactate concentration.

Results

Eight hundred and four healthy participants (93%) fulfilled the exercise test until voluntary exhaustion. There were no sex-related differences in HR_max, RER, or Borg Scale rating, whereas blood lactate concentration was 18% lower in women (P<0.001). Forty-two percent of the participants achieved a plateau in VO₂; these individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and 5% higher blood lactate concentration (P = 0.047) compared with participants who did not reach a VO₂ plateau. When using RER ≥1.15 or blood lactate concentration ≥8.0 mmol•L^–1, VO_2max was 4% (P = 0.012) and 10% greater (P<0.001), respectively. A blood lactate concentration ≥8.0 mmol•L^–1 excluded 63% of the participants in the 50–85-year-old cohort.

Conclusions

A range of typical end criteria are presented in a random sample of subjects aged 20–85 years. The choice of end criteria will have an impact on the number of the participants as well as the VO_2max outcome. Suggestions for new recommendations are given.     

Cytokine gene expression in human skeletal muscle during concentric contraction: evidence that IL-8, like IL-6, is influenced by glycogen availability

To determine the expression and induction of cytokines in human skeletal muscle during concentric contractions, eight males performed 60 min of bicycle exercise, with either a normal (Con) or reduced (Lo Gly) preexercise intramuscular glycogen content. Muscle biopsy samples were obtained before and after exercise and analyzed for glycogen and the mRNA expression of 13 cytokines. Resting muscle glycogen was higher (P < 0.05) in Con compared with Lo Gly and was reduced (P < 0.05) to 102 +/- 32 vs. 17 +/- 5 mmol U glycosyl/kg dry mass for Con and Lo Gly, respectively. We detected mRNA levels in human skeletal muscle for five cytokines, namely interleukin (IL)-1 beta, IL-6, IL-8, IL-15, and tumor necrosis factor-alpha. However, muscle contraction increased (P < 0.05) the mRNA expression of IL-6 and IL-8 alone. In addition, the fold change for both IL-8 and IL-6 was markedly higher (P < 0.05) in Lo Gly compared with Con. Given these results, we analyzed venous blood samples, obtained before and during exercise, for IL-6 and IL-8. Plasma IL-6 was not different at rest, and although the circulating concentration of this cytokine increased (P < 0.05) it increased to a greater extent (P < 0.05) throughout exercise in Lo Gly. In contrast, plasma IL-8 was not affected by exercise or treatment. These data demonstrate that cytokines are not ubiquitously expressed in skeletal muscle and that only IL-6 and IL-8 mRNA are increased during contraction of this mode and duration. Furthermore, the mRNA abundance of IL-6 and IL-8 appears to be influenced by glycogen availability in the contracting muscle.     

Fat Oxidation,Fitness and Skeletal Muscle Expression of Oxidative/Lipid Metabolism Genes in South Asians: Implications for Insulin Resistance?

Background

South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.

Methodology/Principal Findings

Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO_2max (40.6±6.6 vs 52.4±5.7 ml.kg⁻¹.min⁻¹, p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg.kg⁻¹.min⁻¹ at 55% VO_2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg.kg⁻¹.min⁻¹ at 25 ml O₂.kg⁻¹.min⁻¹, p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO_2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO_2max or fat oxidation during exercise explaining 10–13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.

Conclusions/Significance

These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.     

Effects of continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content in rat skeletal muscle.

Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep involvement in enhanced insulin action and GLUT-4 protein content after exercise training. The present study examined the chronic effects of a continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen content, AMPK, and insulin signaling in skeletal muscle. Rats were divided randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes of rest. The 10-day exercise training resulted in a significant increase in the GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex rats. Taken together, we suggest that the maintenance of glycogen depletion after exercise by continuous low carbohydrate diet results in the increment of the GLUT-4 protein content in skeletal muscle.     

Decreased Eccentric Exercise-Induced Macrophage Infiltration in Skeletal Muscle after Supplementation with a Class of Ginseng-Derived Steroids

Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68⁺ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163⁺ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68⁺ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.     

Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

It has been suggested that human mitochondrial variants influence maximal oxygen uptake (VO_2max). Whether mitochondrial respiratory capacity per mitochondrion (intrinsic activity) in human skeletal muscle is affected by differences in mitochondrial variants is not known. We recruited 54 males and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO_2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO_2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present.     

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes’ responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HR_max) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices – maximal oxygen uptake (VO_2max, maximum heart rate (HR_max), maximum ventilation (V_Emax) and anaerobic threshold (AT) – before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO_2max (both p<0.001), and increased V_Emax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO_2max (p=0.029 and p=0.026), and V_Emax (p=0.005). As the result of training, significantly greater improvements in VO_2max, V_Emax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.     

Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension

Background

Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH.

Methods

The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls.

Results

PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO₂ max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output.

Conclusion

Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.     

Additive effects of training and high-fat diet on energy metabolism during exercise

This study was conducted to obtain additional information about the adaptations after 12 wk of high-fat diet (HFD) per se or HFD combined with endurance training in the rat using a two [diet: carbohydrate (CHO) or HFD] by two (training: sedentary or trained) by two (condition at death: rested or exercised) factorial design. Adaptation to prolonged HFD increases maximal O2 uptake (VO2max; 13%, P less than 0.05) and submaximal running endurance (+64%, P less than 0.05). This enhancement in exercise capacity could be attributed to 1) an increase in skeletal muscle aerobic enzyme activities (3-hydroxyacyl-CoA dehydrogenase and citrate synthase in soleus and red quadriceps) or 2) a decrease in liver glycogen breakdown in response to 1 h exercise at 80% VO2max. When training is superimposed to HFD, the most prominent finding provided by this study is that the diet-induced effects are cumulative with the well-known training effect on VO2max, exercise endurance, oxidative capacity of red muscle, and metabolic responses to exercise, with a further reduction in liver glycogen breakdown.