Hisashi Naito

Juntendo University, Edo, Tokyo, Japan

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Publications (141)393.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of icing or heat stress on the regeneration of injured soleus muscle were investigated in male Wistar rats. Bupivacaine was injected into soleus muscles bilaterally to induce muscle injury. Icing (0 °C, 20 min) was carried out immediately after the injury. Heat stress (42 °C, 30 min) was applied every other day during 2-14 days after the bupivacaine injection. Injury-related increase in collagen deposition was promoted by icing. However, the level of collagen deposition in heat-stressed animals was maintained at control levels throughout the experimental period and was significantly lower than that in icing-treated animals at 15 and 28 days after bupivacaine injection. Furthermore, the recovery of muscle mass, protein content, and muscle fiber size of injured soleus toward control levels was partially facilitated by heat stress. These results suggest that, compared with icing, heat stress may be a beneficial treatment for successful muscle regeneration at least by reducing fibrosis.
    No preview · Article · Jan 2016 · The Journal of Physiological Sciences
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    ABSTRACT: The study described herein aimed to examine changes in HDAC4 and its downstream targets in immobilization-induced rat skeletal muscle atrophy. Eleven male Wistar rats were used, and one hindlimb was immobilized in the plantar flexion position using a plaster cast. The contralateral, non-immobilized leg served as an internal control. After 10 days, the gastrocnemius muscles were removed from both hindlimbs. Ten days of immobilization resulted in a significant reduction (-27.3 %) in gastrocnemius muscle weight. A significant decrease in AMPK phosphorylation was also observed in nuclear fractions from immobilized legs relative to the controls. HDAC4 expression was significantly increased in immobilized legs in both the cytoplasmic and nuclear fractions. Moreover, Myogenin and MyoD mRNA levels were upregulated in immobilized legs, resulting in increased Atrogin-1 mRNA expression. Our data suggest that nuclear HDAC4 accumulation is partly related to immobilization-induced muscle atrophy.
    No preview · Article · Jan 2016 · The Journal of Physiological Sciences
  • H. Ozaki · T. Kitada · T. Abe · S. Machida · H. Naito · S. Katamoto

    No preview · Article · Dec 2015
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    Tomoharu Kitada · Shuichi Machida · Hisashi Naito
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    ABSTRACT: Aims To investigate the relationship between muscle oxygenation (specifically, the levels of oxygenated haemoglobin and myoglobin [oxyHb/Mb]) during maximal running and muscle fibre composition, and to determine whether muscle fibre composition can be non-invasively estimated from oxyHb/Mb levels during maximal running. Methods Eight male runners (, 60.9± 4.6 mL·kg−1·min−1) performed an incremental running test on a treadmill. OxyHb/Mb levels of the vastus lateralis during maximal running were measured by near-infrared spectroscopy (NIRS). Muscle fibre composition of the vastus lateralis was determined from muscle biopsy samples from the same region measured by NIRS, and the fibre types were classified as type I, type IIa, or type IIb fibres using traditional pH-sensitive ATPase staining. Type I and type IIa fibres together were defined as oxidative fibres. Results OxyHb/Mb levels during running were lowest at exhaustion in all participants. OxyHb/Mb levels at exhaustion were positively correlated with the percentages of type I fibres (r=0.755, p<0.05) and oxidative fibres (r=0.944, p<0.01). Conclusions We conclude that higher oxyHb/Mb levels at exhaustion during maximal running are correlated with a higher percentage of oxidative fibres, indicating the potential importance of oxidative fibres in the maintenance of oxyHb/Mb levels during maximal running. Additionally, muscle fibre composition could be non-invasively estimated from oxyHb/Mb levels during maximal running tests in runners.
    Preview · Article · Nov 2015
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    ABSTRACT: We examined the effect of repeated heat stress on muscle atrophy, and apoptotic and proteolytic regulation in unloaded rat slow- and fast-type skeletal muscles. Forty male Wistar rats (11 week-old) were divided into control (CT), hindlimb unweighting (HU), intermittent weight-bearing during HU (HU + IWB), and intermittent weight-bearing with heat stress during HU (41-41.5°C for 30 min; HU + IWB + HS) groups. The HU + IWB + HS and HU + IWB groups were released from unloading for 1 h every second day, during which the HU + IWB + HS group underwent the heating. Our results revealed that repeated bouts of heat stress resulted in protection against disuse muscle atrophy in both soleus and plantaris muscles. This heat stress-induced protection against disuse-induced muscular atrophy may be partially due to reduced apoptotic activation in both muscles, and decreased ubiquitination in only the soleus muscle. We concluded that repeated heat stress attenuated skeletal muscle atrophy via suppressing apoptosis but the response to proteolytic systems depend on the muscle phenotype.
    Preview · Article · Oct 2015
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    ABSTRACT: Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against MV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control, 2) single bout of whole-body heat stress, 3) repeated bouts of whole-body heat stress, 4) 12 hours CMV, 5) single bout of whole-body heat stress 24 hours prior to CMV, and 6) repeated bouts of whole-body heat stress 1, 3, and 5 days prior to 12 hours of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear, this heat stress-induced protection against MV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.
    No preview · Article · Sep 2015 · Journal of Applied Physiology
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    ABSTRACT: Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.
    No preview · Article · Jul 2015 · Molecular and Cellular Biochemistry
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    ABSTRACT: Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: Low-load voluntary exercise can induce muscle hypertrophy and strength gain when combined with blood flow restriction (BFR) in working muscles. However, it is unknown whether such hypertrophy and strength gain can be induced by involuntary muscle contractions triggered via low-intensity neuromuscular electrical stimulation (NMES), combined with BFR. The purpose of this article was to investigate whether low-intensity NMES combined with BFR could elicit muscle hypertrophy and strength gain in the quadriceps. Eight untrained young males (means ± SEs; age 26.2±0.7 years, height 1.74±0.02 m, body weight 71.4±4.8 kg) received 23 min of unilateral low-intensity (5-10% of maximal voluntary contraction) NMES, twice per day, 5 days per week, for 2 weeks, with treatment of one leg being combined with BFR (NMES-BFR) and the other leg receiving NMES alone (NMES-CON). Quadriceps muscle thickness (MT) and isometric and isokinetic strength were measured before and every week throughout the training and detraining periods. In NMES-BFR legs, MT increased after 2 weeks of training (+3.9%) and decreased after 2 weeks of detraining (-3.0%). NMES-BFR training also increased maximal knee extension strength in isometric (+14.2%) and isokinetic (+7.0% at 90°/s, +8.3% at 180°/s) voluntary contractions. In addition, maximal isometric strength decreased (-6.8%), whereas no large fall (-1.9% at 90°/s, -0.6% at 180°/s) in isokinetic maximal strength was evident after 2 weeks of detraining. In NMES-CON legs, no prominent change was observed; there was a negligible effect on isometric strength. Low- intensity NMES combined with BFR induces muscle hypertrophy and strength gain in untrained young males.
    No preview · Article · Jun 2015 · Medicine and science in sports and exercise
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    Full-text · Dataset · May 2015

  • No preview · Article · Apr 2015 · The FASEB Journal
  • Akihiro Sakamoto · Hisashi Naito · Chin Moi Chow
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    ABSTRACT: Hyperventilation, implemented during recovery of repeated maximal sprints, has been shown to attenuate performance decrement. This study evaluated the effects of hyperventilation, using strength exercises, on muscle torque output and EMG amplitude. Fifteen power-trained athletes underwent maximal isokinetic knee extensions consisting of 12 repetitions × 8 sets at 60°/s and 25 repetitions × 8 sets at 300°/s. The inter-set interval was 40 s for both speeds. For the control condition, subjects breathed spontaneously during the interval period. For the hyperventilation condition, subjects hyperventilated for 30 s before each exercise set (50 breaths/min, PETCO2: 20-25 mmHg). EMG was recorded from the vastus medialis and lateralis muscles to calculate the mean amplitude for each contraction. Hyperventilation increased blood pH by 0.065-0.081 and lowered PCO2 by 8.3-10.3 mmHg from the control values (P < 0.001). Peak torque declined with repetition and set numbers for both speeds (P < 0.001), but the declining patterns were similar between conditions. A significant, but small enhancement in peak torque was observed with hyperventilation at 60°/s during the initial repetition phase of the first (P = 0.032) and fourth sets (P = 0.040). EMG amplitude also declined with set number (P < 0.001) for both speeds and muscles, which was, however, not attenuated by hyperventilation. Despite a minor ergogenic effect in peak torque at 60°/s, hyperventilation was not effective in attenuating the decrement in torque output at 300°/s and decrement in EMG amplitude at both speeds during repeated sets of maximal isokinetic knee extensions.
    No preview · Article · Feb 2015 · Arbeitsphysiologie
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    ABSTRACT: This paper reviews the existing literature about muscle hypertrophy resulting from various types of training to document the significance of mechanical and metabolic stresses, and to challenge the conventional ideas of achieving hypertrophy that exclusively rely on highload resistance training. Low-load resistance training can induce comparable hypertrophy to that of high-load resistance training when each bout or set is performed until lifting failure. This is attributable to the greater exercise volume and metabolic stress achieved with low-load exercise at lifting failure, which, however, results in a prolonged exercise bout. Endurance exercises (walking and cycling) at moderate intensity are also capable of eliciting muscle hypertrophy, but at much slower rates (months rather than weeks) in limited muscle or age groups. Blood flow restriction (BFR) in working muscles, however, accelerates the development of metabolic fatigue, alleviating the time consuming issue associated with low-load or endurance training. These alternative training methods, however, cannot completely replace conventional high-load resistance training, which provides superior strength gain as well as performance improvement even for trained individuals. The alternative approaches, therefore, may be considered for those who are less enthusiastic or under certain medical conditions, or who have limited or no access to proper equipment. However, people should be aware that low-load resistance training or endurance training entails substantial effort and/or discomfort at lifting failure or with BFR. Understanding the advantages and disadvantages of each method will help in assigning the most suitable training program for each client’s goals and needs.
    No preview · Article · Feb 2015 · Tairyoku kagaku. Japanese journal of physical fitness and sports medicine
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    Eisuke Hiruma · Shizuo Katamoto · Hisashi Naito

    Preview · Article · Jan 2015
  • A. Sakamoto · H. Naito · C.M. Chow

    No preview · Article · Dec 2014
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    ABSTRACT: Background The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI.
    Full-text · Article · Sep 2014 · BMC Public Health
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    ABSTRACT: Mechanical ventilation (MV) is a life-saving intervention in patients who are incapable of maintaining adequate pulmonary gas exchange due to respiratory failure or other disorders. However, prolonged MV is associated with the development of respiratory muscle weakness. We hypothesized that a single exposure to whole-body heat stress would increase diaphragm expression of heat shock protein 72 (HSP72) and that this treatment would protect against MV-induced diaphragmatic atrophy. Adult male Wistar rats (n = 38) were randomly assigned to one of four groups: an acutely anesthetized control group (CON) with no MV; 12-h controlled MV group (CMV); 1-h whole-body heat stress (HS); or 1-h whole-body heat stress 24 h prior to 12-h controlled MV (HSMV). Compared to CON animals, diaphragmatic HSP72 expression increased significantly in the HS and HSMV groups (P < 0.05). Prolonged MV resulted in significant atrophy of type I, type IIa, and type IIx fibers in the costal diaphragm (P < 0.05). Whole-body heat stress attenuated this effect. In contrast, heat stress did not protect against MV-induced diaphragm contractile dysfunction. The mechanisms responsible for this heat stress-induced protection remain unclear, but may be linked to increased expression of HSP72 in the diaphragm.
    Preview · Article · Jul 2014 · Journal of Applied Physiology
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    ABSTRACT: Purpose: Body weight in young growing and young adult animals was reduced by a high dietary density of whey protein concentrate; however, it is unclear whether dietary proteins similarly affect body weight in aging animals. Here, we examined whether whey protein or whey peptide ingestion suppressed body fat accumulation and affected protein expression and phosphorylation in skeletal muscle in aging mice. Methods: Twenty-six male senescence-accelerated mouse prone 6 (SAMP6) mice were assigned randomly to three dietary treatment groups: 18.7% casein control (CON), 18.7% whey protein (WPR), and 18.7% whey peptide (WPE). After 28 weeks of treatment, skeletal tissues were dissected and weighed for analysis. Western blotting was performed to examine the expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and adipose triglyceride lipase (ATGL) in quadriceps muscles. Results: Body (CON: 47.6 ± 2.2 g, WPR: 48.2 ± 2.7 g, WPE: 38.3 ± 2.0 g) and relative white adipose tissue (CON: 38.5 ± 3.5 mg/g, WPR: 43.8 ± 4.0 mg/g, WPE: 21.1 ± 4.4 mg/g) weights were lower in the WPE group compared with the other two groups (p < 0.05), and no significant differences were observed between the CON and WPR groups. The relative weights of tibialis anterior muscle (CON: 1.04 ± 0.04 mg/g, WPR: 0.97 ± 0.03 mg/g, 1.23 ± 0.05 mg/g) and gastrocnemius muscle (CON: 3.02 ± 0.12 mg/g, WPR: 2.92 ± 0.15 mg/g, WPE: 3.65 ± 0.18 mg/g) were higher in the WPE group compared with the other groups (p < 0.05). The phosphorylation of AMPK (WPR: 1.03 ± 0.11, WPE: 1.36 ± 0.12; fold change from control) and ACC (WPR: 1.08 ± 0.07, WPE: 1.18 ± 0.05; fold change from control) in WPE was higher than in CON (p < 0.05). There were no significant differences in the expression levels of ATGL among the three groups. Conclusions: These data suggest that a normal (or moderate excess) dietary density of whey peptide attenuates body fat accumulation via upregulation of fatty acid oxidation in skeletal muscle in aging mice.
    No preview · Article · Jul 2014 · European Journal of Nutrition
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    ABSTRACT: 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: 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 non-obese 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 euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by qRT-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 (L-GIR) subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses. Results: Compared with the L-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 non-obese men.
    Full-text · Article · Jun 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Walking combined with blood flow reduction (BFR-walk) elicits muscle hypertrophy. However, the skeletal muscle intracellular signaling behind this response is currently unknown. To investigate the effects of BFR-walk on mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in young men. Six young men performed 20 minutes of treadmill walking at 55 % of their predetermined maximum oxygen uptake. A pressure cuff belt was applied to the most proximal thigh of only one leg (BFR-Leg, external compression was 240 mmHg) whereas the other leg (CON-Leg) was without BFR during walking. Muscle biopsies were taken from the vastus lateralis of the CON-Leg before exercise and in both legs 3 hours after exercise. Erk1/2 phosphorylation levels were significantly (p<0.05) increased after exercise in both legs, however, only the BFR-Leg saw an increased phosphorylation of p38. For mTOR signaling, there were no changes in Akt, mTOR, or S6K1 phosphorylation levels before or after walking. However, eEF2 phosphorylation level was significantly (p<0.05) lower for the BFR-Leg 3 hours after walking compared with CON-Leg. BFR-walk exercise may activate some intracellular signaling cascades that are associated with muscle hypertrophy in young men. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2014 · Acta Physiologica

Publication Stats

2k Citations
393.85 Total Impact Points


  • 2001-2015
    • Juntendo University
      • • Institute of Health and Sports Science and Medicine
      • • Department of Sports Science
      • • Graduate School of Health and Sports Science
      • • Department of Health Science
      Edo, Tokyo, Japan
  • 2008
    • Hirosaki Gakuin University
      Aomori, Aomori, Japan
  • 1998-2002
    • University of Florida
      • Center for Exercise Science
      Gainesville, Florida, United States