The Impact of 5-Aminolevulinic Acid Supplementation on Redox Balance and Aerobic Capacity.

We examined the impact of 5-aminolevulinic acid (5-ALA) and sodium-ferrous-citrate supplementation on aerobic capacity and redox balance through a placebo-controlled, double-blind trial. Fourteen healthy volunteers were randomly assigned to Pla + ALA (4-week placebo followed by 4-week 5-ALA supplementation) or ALA + Pla (4-week 5-ALA supplement followed by a 4-week placebo) group and administered 5-ALA (25 mg/day) or placebo once daily. The participants underwent submaximal incremental cycling tests at weeks 0, 2, 4, 6, and 8. In the cycling test at week 0, individual load-intensity stages required for blood lactate levels >2 mmol/L (lactate threshold, LT) and 4 mmol/L (onset of blood lactate accumulation, OBLA) were determined. The heart rate (HR), blood lactate (La), and oxidative stress markers (diacron reactive oxygen metabolite, d-ROMs; biological antioxidant potential, BAP) were measured at resting, LT, and OBLA states in each cycling test. Marker values were not significantly different between the groups. HR, La, and d-ROMs at resting, LT, and OBLA states were not significantly different among the conditions. BAP and BAP/d-ROMs ratios were significantly different in the OBLA state at week 4 of the 5-ALA group compared with that of the placebo group (p < 0.05). In conclusion, 5-ALA supplementation might improve redox balance during high-intensity aerobic exercise.

Endurance Runners with Intramyocellular Lipid Accumulation and High Insulin Sensitivity Have Enhanced Expression of Genes Related to Lipid Metabolism in Muscle.

CONTEXT: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. DESIGN AND SETTING: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. RESULTS: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, "RESPONSE TO LIPID" was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2-3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. CONCLUSIONS: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.

Association between expression of FABPpm in skeletal muscle and insulin sensitivity in intramyocellular lipid-accumulated nonobese men.

CONTEXT: Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance. OBJECTIVE: The objective of the study was to investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects. DESIGN AND SETTING: The study subjects were 36 nonobese healthy men. Their IMCL levels were measured by (1)H-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses. RESULTS: Compared with the low-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1-overexpressed myotubes. CONCLUSIONS: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.

Effects of training volume on strength and hypertrophy in young men.

Knowledge of the effects of training volume on upper limb muscular strength and hypertrophy is rather limited. In this study, both arms of the same subject were trained in a crossover-like design with different training volumes (1 or 3 sets) to eliminate the effects of genetic variation and other individual differences. The purpose of this study was to investigate the effects of training volume on muscular strength and hypertrophy in sedentary, untrained young Japanese men. Eight subjects (age, 25.0 ± 2.1 years; body mass, 64.2 ± 7.9 kg; height, 171.7 ± 5.1 cm) were recruited. The subjects trained their elbow flexor muscles twice per week for 12 consecutive weeks using a seated dumbbell preacher curl. The arms were randomly assigned to training with 1 or 3 sets. The training weight was set at 80% of 1 repetition maximum for all sets. The 3-set protocol increased cross-sectional area significantly more than did 1 set (1 set, 8.0 ± 3.7%; 3 sets, 13.3 ± 3.6%, p < 0.05). Furthermore, gains in strength with the 3-set protocol tended to be greater than those with 1 set (1 set, 20.4 ± 21.6%; 3 sets, 31.7 ± 22.0%, p = 0.076). Based on the results, the authors recommend 3 sets for sedentary untrained individuals. However, this population should incorporate light training days of 1 set into their training program to prevent overtraining and ensure adherence. The findings are relevant for the sedentary, untrained young male population and must be interpreted within the context of this study.

Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle.

This study investigated the effect of heat stress (HS) on mammalian target of rapamycin (mTOR) signaling involved in translation initiation after resistance exercise in human skeletal muscle. Eight young male subjects performed four sets of six maximal repetitions of knee extension exercises, with or without HS, in a randomized crossover design. HS was applied to the belly of the vastus lateralis by using a microwave therapy unit prior to and during exercise. Muscle biopsies were taken from the vastus lateralis before, immediately after, and 1 h after exercise. HS significantly increased the phosphorylation of Akt/PKB, mTOR, and ribosomal protein S6 at 1 h after exercise (P < 0.05), and the 4E-BP1 phosphorylation level, which had initially decreased with exercise, had recovered by 1 h after exercise with HS. In addition, the phosphorylation of ribosomal S6 kinase 1 was significantly increased immediately after exercise with HS (P < 0.05). These results indicate that HS enhances mTOR signaling after resistance exercise in human skeletal muscle.

Determinants of intramyocellular lipid accumulation after dietary fat loading in non-obese men.

UNLABELLED: Aims/Introduction: Accumulation of intramyocellular lipid (IMCL) is associated with insulin resistance. However, the factors affecting the change in IMCL remain to be elucidated. The aim of the present study was to determine the factors that influence the change in IMCL level after high-fat loading. MATERIALS AND METHODS: The study subjects were 37 non-obese men. Each subject consumed a high-fat diet for 3 days after a normal-fat diet for 3 days. After each diet program, IMCL levels in the tibialis anterior (TA-IMCL) and soleus (SOL-IMCL) were measured by proton magnetic resonance spectroscopy. Glucose infusion rate (GIR) was evaluated by euglycemic hyperinsulinemic clamp as an index of peripheral insulin sensitivity. RESULTS: The high-fat diet significantly increased TA-IMCL and SOL-IMCL by ∼30 and ∼20%, respectively (P < 0.05), whereas it did not significantly alter GIR. The increase in SOL-IMCL, but not in TA-IMCL, negatively correlated with serum high molecular weight (HMW)-adiponectin (r = -0.36, P < 0.05) and HMW-/total-adiponectin ratio (r = -0.46, P < 0.05). Although high-fat diet-related changes in SOL-IMCL showed high inter-individual variations, in subjects doing exercise, changes in SOL-IMCL (r = 0.55, P < 0.05) and TA-IMCL (r = 0.61, P < 0.05) positively correlated with daily physical activity level. In contrast, in sedentary subjects, changes in SOL-IMCL (r = -0.50, P < 0.01) and TA-IMCL (r = -0.48, P < 0.05) negatively correlated with daily physical activity. CONCLUSIONS: HMW-adiponectin and daily physical activity are determinants of IMCL accumulation by a high-fat diet. Intriguingly, the effect of daily physical activity on the change in IMCL depends on the level of regular exercise. (J Diabetes Invest,doi: 10.1111/j.2040-1124.2010.00091.x, 2011).

Effect of heat preconditioning by microwave hyperthermia on human skeletal muscle after eccentric exercise.

The purpose of this study was to clarify whether heat preconditioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a microwave hyperthermia unit (150 W, 20 min) that was randomly applied to one of the subject's arms (MW); the other arm was used as a control (CON). One day after heat preconditioning, the subjects performed 24 maximal isokinetic eccentric contractions of the elbow flexors at 30°·s(-1) (ECC1). One week after ECC1, the subjects repeated the procedure (ECC2). After each bout of exercise, maximal voluntary contraction (MVC), range of motion (ROM) of the elbow joint, upper arm circumference, blood creatine kinase (CK) activity and muscle soreness were measured. The subjects experienced both conditions at an interval of 3 weeks. MVC and ROM in the MW were significantly higher than those in the CON (p < 0.05) for ECC1; however, the heat preconditioning had no significant effect on upper arm circumference, blood CK activity, or muscle soreness following ECC1 and ECC2. Heat preconditioning may protect human skeletal muscle from eccentric exercise-induced muscle damage after a single bout of eccentric exercise but does not appear to promote the repeated bout effect after a second bout of eccentric exercise. Key pointsThere have been few studies about the effects of heat preconditioning on muscle damage caused by eccentric exercise and the repeated bout effect after a second bout of eccentric exercise.Heat preconditioning with microwave hyperthermia may attenuate eccentric exercise-induced muscle damage.Heat preconditioning does not enhance the repeated bout effect.

Microwave hyperthermia treatment increases heat shock proteins in human skeletal muscle.

OBJECTIVE: To test the hypothesis that microwave hyperthermia treatment (MHT) increases heat shock proteins (HSPs) in the human vastus lateralis muscle. METHODS: Four untrained healthy male volunteers participated in this study. The lateral side of the thigh of one leg (heated leg) was heated with a microwave generator (2.5 GHz, 150 W) for 20 min. At 1 day after the MHT, a muscle sample was taken from the heated leg. A control sample was taken from the unheated leg on another day of the MHT. For both legs, HSP90, HSP72 and HSP27 levels were compared. RESULTS: The HSP90, HSP72 and HSP27 levels in heated legs were significantly higher than those in control legs (p<0.05). CONCLUSIONS: Application of MHT can increase the levels of several HSPs in human skeletal muscle.

Changes in muscle temperature induced by 434 MHz microwave hyperthermia.

OBJECTIVE: To investigate the changes in temperature of human muscle during microwave hyperthermia. METHODS: Skin surface and muscle temperatures were measured in 11 healthy adult men (mean (SD) age 24.3 (2.2) years; height 174.2 (6.1) cm; weight 70.0 (5.3) kg) during a 30 min exposure of the thigh to 434 MHz microwave hyperthermia. Skin temperature was maintained at the pilot temperature of 40 degrees C, and the temperature of the water in the bolus was 38 degrees C. The peak power output was set at 60 W and controlled automatically to maintain the pilot temperature. The temperature was measured in the vastus lateralis muscle at an average muscle depth of 2.0 (0.2) cm, using a 23 G Teflon-shielded thermocouple. Biopsy specimens were obtained for light microscopy from three subjects. A muscle-equivalent phantom was used to evaluate the vertical heating pattern. RESULTS: Both skin and muscle temperatures increased from baseline, and muscle temperature was higher than skin temperature (skin temperature 39.2 (0.5) degrees C, temperature rise 5.0 (1.5) degrees C; muscle temperature 43.7 (0.8) degrees C, temperature rise 8.9 (1.4) degrees C). At the end of the hyperthermia treatment, muscle temperature decreased to 39.8 (0.9) degrees C, but was still 4.8 (1.5) degrees C higher than the baseline. No signs of muscle damage were observed on the basis of the blood creatine kinase activity and histological sections. CONCLUSIONS: The results show that the 434 MHz microwave hyperthermia treatment increased and maintained muscle temperature locally by 6.3-11.4 degrees C without muscle damage. These findings suggest that the microwave hyperthermia system provides effective and safe treatment.