Michihiro Kon

Profiling of circulating microRNAs after a bout of acute resistance exercise in humans.

Recent studies have revealed a new aspect of physiological regulation in which microRNAs (miRNAs) play fundamental roles in diverse biological and pathological processes. Furthermore, it was recently discovered that miRNAs are stably secreted into blood and that circulating miRNAs may play important roles in cell–cell communication. Here, we examined whether the circulating miRNA profile is affected by acute resistance exercise. Twelve males performed a resistance exercise session (bench press and leg press), consisting of five sets of 10 repetitions at 70% of maximum strength, with a 1 min rest between sets. Blood samples were taken before exercise, and at 0 and 60 min, 1 day, and 3 days after exercise. The circulating miRNA profile was determined by microarray analysis. Quantitative real-time PCR confirmed that the miR-149* level increased three days after resistance exercise. In contrast, the miR-146a and miR-221 levels decreased three days after resistance exercise. Our findings suggest that circulating miRNA levels change in response to acute resistance exercise, and miRNAs may play important roles in resistance-exercise-induced adaptation.

Effects of systemic hypoxia on human muscular adaptations to resistance exercise training

Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross‐sectional area (CSA), one‐repetition maximum (1RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), citrate synthase (CS) activity, nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia‐inducible factor‐1 (HIF‐1), and capillary‐to‐fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group (NRT, n = 7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n = 9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1RM for bench‐press and leg‐press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle.

Effects of acute hypoxia on metabolic and hormonal responses to resistance exercise

INTRODUCTION Several recent studies have shown that resistance exercise combined with vascular occlusion effectively causes increases in muscular size and strength. Researchers speculated that the vascular occlusion-induced local hypoxia may contribute to the adaptations via promoting anabolic hormone secretions stimulated by local accumulation of metabolic subproducts. Here, we examined whether acute systemic hypoxia affects metabolic and hormonal responses to resistance exercise. METHODS Twelve male subjects participated in two experimental trials: 1) resistance exercise while breathing normoxic air [normoxic resistance exercise (NR)] and 2) resistance exercise while breathing 13% oxygen [hypoxic resistance exercise (HR)]. The resistance exercises (bench press and leg press) consisted of 10 repetitions for five sets at 70% of maximum strength with 1-min rest between sets. Blood lactate, serum growth hormone (GH), epinephrine (E), norepinephrine (NE), insulin-like growth factor 1, testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures, 15 min after the exposures, and at 0, 15, 30, and 60 min after the exercises. RESULTS Lactate significantly increased after exercises in both trials (P < 0.05). In the HR trial, GH and cortisol significantly increased after the exercise (P < 0.05) but not in the NR trial. The E, NE, insulin-like growth factor 1, and testosterone significantly increased after the exercises in both trials (P < 0.05). The mean values of lactate, GH, E, and NE after exercises were significantly higher in the HR trial than those in the NR trial (P < 0.05). CONCLUSIONS These findings suggest that resistance exercise in hypoxic condition caused greater accumulation of metabolites and strong anabolic hormone response.

Effects of Low-intensity Resistance Exercise Under Acute Systemic Hypoxia on Hormonal Responses

Kon, M, Ikeda, T, Homma, T, and Suzuki, Y. Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses. J Strength Cond Res 26(3): 611–617, 2012—Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.

Hormonal and metabolic responses to repeated cycling sprints under different hypoxic conditions

OBJECTIVE Sprint exercise and hypoxic stimulus during exercise are potent factors affecting hormonal and metabolic responses. However, the effects of different hypoxic levels on hormonal and metabolic responses during sprint exercise are not known. Here, we examined the effect of different hypoxic conditions on hormonal and metabolic responses during sprint exercise. DESIGN Seven male subjects participated in three experimental trials: 1) sprint exercise under normoxia (NSE); 2) sprint exercise under moderate normobaric hypoxia (16.4% oxygen) (HSE 16.4); and 3) sprint exercise under severe normobaric hypoxia (13.6% oxygen) (HSE 13.6). The sprint exercise consisted of four 30s all-out cycling bouts with 4-min rest between bouts. Glucose, free fatty acids (FFA), blood lactate, growth hormone (GH), epinephrine (E), norepinephrine (NE), and insulin concentrations in the HSE trials were measured before exposure to hypoxia (pre 1), 15 min after exposure to hypoxia (pre 2), and at 0, 15, 30, 60, 120, and 180 min after the exercise performed in hypoxia. The blood samples in the NSE trial were obtained in normoxia at the same time points as the HSE trials. RESULTS Circulating levels of glucose, FFA, lactate, GH, E, NE, and insulin significantly increased after all three exercise trials (P < 0.05). The area under the curve (AUC) for GH was significantly higher in the HSE 13.6 trial than in the NSE and HSE 16.4 trials (P < 0.05). A maximal increase in FFA concentration was observed at 180 min after exercise and was not different between trials. CONCLUSION These findings suggest that severe hypoxia may be an important factor for the enhancement of GH response to all-out sprint exercise.

Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle.

The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT-/y) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT-/y and wild type (CrT+/y) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) were also determined as were the rates of in vitro Cr biosynthesis. CrT-/y mice muscle contained measurable (22.3 ± 4.3 mmol.kg−1 dry mass), but markedly reduced (P < 0.05) TCr levels compared with CrT+/y mice (125.0 ± 3.3 mmol.kg−1 dry mass). AGAT gene and protein expression were higher (~3 fold; P < 0.05) in CrT−/y mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P < 0.05) in CrT−/y mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr may be at least partly due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT−/y mice. Of note, the up regulation of Cr biosynthesis in CrT−/y mice muscle was unable to fully restore Cr levels to that found in wild type muscle.

Effects of systemic hypoxia on human muscular adaptations to resistance exercise training: Reply from the authors

This study investigated the effect of resistance exercise training performed under systemic hypoxia or normoxia on biochemical and molecular muscular adaptations in healthy male subjects. Our findings demonstrate that resistance training under systemic hypoxia led not only to muscle hypertrophy, but most interestingly, to a greater increase in muscular endurance. This increase in muscular endurance was potentially caused by the increased angiogenesis as determined by capillary‐to‐fiber ratio.

Coenzyme Q10 supplementation downregulates the increase of monocytes expressing toll-like receptor 4 in response to 6-day intensive training in kendo athletes.

This study examined changes in toll-like receptor 4 (TLR-4)-expressing monocytes and lymphocyte subpopulations in response to continuous intensive exercise training in athletes, as well as the effect of coenzyme Q10 (CoQ10) supplementation on these changes. Eighteen male elite kendo athletes in Japan were randomly assigned to a CoQ10-supplementation group (n = 9) or a placebo-supplementation group (n = 9) using a double-blind method. Subjects in the CoQ10 group took 300 mg CoQ10 per day for 20 days. Subjects in the placebo group took the same dosage of placebo. All subjects practiced kendo 5.5 h per day for 6 consecutive days during the study period. Blood samples were collected 2 weeks before training, on the first day (day 1), third day (day 3), and fifth day of training (day 5), and 1 week after the training period (post-training) to ascertain TLR-4(+)/CD14(+) monocyte and lymphocyte subpopulations (CD3(+), CD4(+), CD8(+), CD28(+)/CD4(+), CD28(+)/CD8(+), and CD56(+)/CD3(-) cells) using flow cytometry analysis. The group × time interaction for TLR-4(+)/CD14(+) cells did not reach significance (p = 0.08). Within the CoQ10 group, the absolute number of TLR-4(+)/CD14(+) cells was significantly higher only at day 5. The placebo group showed a significant increase in the absolute number of TLR-4(+)/CD14(+) cells at day 3, day 5, and post-training (p < 0.05). There was no significant group × time interaction for any lymphocyte subpopulation. CD3(+), CD8(+), and CD56(+)/CD3(-) cells were significantly reduced at day 3 in both groups (p < 0.05). In conclusion, CoQ10 supplementation might downregulate the increase of TLR-4-expressing monocytes in response to continuous strenuous exercise training in kendo athletes.

Effects of a single bout of high-intensity interval exercise on C1q/TNF-related proteins

High-intensity interval training (HIIT) is known to be an effective exercise training regimen to improve energy substrate metabolism and insulin sensitivity. However, the underlying mechanisms of improvement in insulin sensitivity due to HIIT have not yet been fully clarified. C1q/tumor necrosis factor-related protein (CTRP) 1 and CTRP9, which are adiponectin paralogs and novel adipokines, have favorable effects on energy substrate metabolism and insulin sensitivity. The purpose of this study was to investigate the effects of a single bout of HIIT on CTRP1 and CTRP9 secretions in healthy men. Eight healthy male subjects (mean ± SE: age, 23.4 ± 1.1 years; height, 172.1 ± 1.7 cm; body mass, 68.0 ± 2.0 kg; body mass index, 22.9 ± 0.5 kg/m2) participated in this study. They performed a single bout of HIIT consisted of four 30-s maximal cycling bouts with 4 min of rest between bouts using a cycle ergometer. Blood samples were collected before the exercise, at 0 (immediately after the exercise), 15, 30, and 120 min after the single bout of HIIT. Serum CTRP1, CTRP9, and high-molecular-weight (HMW) adiponectin concentrations were measured using enzyme-linked immunosolvent assay kits. CTRP1 concentration significantly increased at 120 min after the HIIT. CTRP9 concentration also significantly increased immediately after the single bout of HIIT. In contrast, there were no significant differences in HMW adiponectin concentration before and after the acute HIIT. These findings suggest that a single bout of HIIT may stimulate CTRP1 and CTRP9 secretions in healthy men.