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Oxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p p 2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

Physical activity is considered a promising behavior to improve cognitive function and academic performance in adolescents. As evidence on the relationship of specific sports activity is not conclusive, this study aimed to determine the longitudinal relationships of different sports to academic performance in adolescents and evaluate the cardiorespiratory fitness mediation effect of these sports. We focused on the demands of complex motor skills and the differences between individual sports vs team sports. Four hundred and sixty-three 7th-grade students (227 girls and 236 boys) were followed up over 2 years. Data regarding participation in sports activities, types of sports activities, academic performance, and cardiorespiratory fitness were obtained at baseline and after a 2-year follow-up. Structural equation modeling revealed that participation in all sports activity was positively associated with improvement of academic performance from baseline to follow-up, and that these associations were mediated by cardiorespiratory fitness gains. Participation in sports activities that require more complex motor skills and individual sports activity was directly associated with an improvement of academic performance from baseline to follow-up. Furthermore, quitting sports activities was negatively associated with academic performance via a reversal in cardiorespiratory fitness gains. These findings indicate that participation in specific sports may have significant benefits for academic performance in adolescents. Although these relationships are presumably mediated by cardiorespiratory fitness, sports activities that require more complex motor skills and individual sports participation may be directly related to academic performance. Considering that quitting sports activities reversed these benefits, sustained participation in sports is important for academic success.

Accepted: 2019-09-18, 資料番号: SA1190110000

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2019-08-26, 資料番号: PA2010049000

Objectives Heterogeneity and homogeneity in the flow-mediated dilation of the human body's individual extremities are not fully understood, and the relationship between flow-mediated dilation and local muscle activity is unclear. We assessed the flow-mediated dilation of four individual extremities and sought to determine the contribution of local muscle activity (evaluated as muscle strength) to the flow-mediated dilation in each extremity. Methods Thirteen healthy young right-handed nonactive males participated. The flow-mediated dilation in the brachial and popliteal arteries at both arms and legs was assessed by ultrasound Doppler. Muscle strength was evaluated as the grip strength and knee extension. Results There was a significant difference in the brachial artery (BA)-FMD values between the subjects' dominant and non-dominant sides (8.0 ± 2.8 vs. 5.5 ± 2.2%, p Conclusion These results demonstrated heterogeneity in the flow-mediated dilation of individual extremities. We observed that local muscle activity can affect the local vascular function. Measurements of vasodilatory function in individual extremities should thus be carefully considered.

Increases in muscle size and strength similar to those obtained with high resistance load can be achieved by combining lower loads with continuous blood flow restriction (BFR). However, high ratings for distress have been reported for continuous BFR. Therefore, we investigated the efficacy (metabolic stress) of BFR applied only during intervals in resistance exercise. Seven healthy men performed three 1-min sets of plantar flexion (30 reps/min) with 1-min rest intervals under 4 conditions: low-load resistance exercise (L, 20% 1-repetition maximum (1RM)) without BFR (L-noBFR), L with BFR during exercise sets (L-exBFR), L with BFR during rest intervals (L-intBFR), and L with continuous BFR during both exercise and rest intervals (L-conBFR). Based on the results of the first experiment, we performed additional protocols using a moderate load (M, 40% 1RM) with intermittent (exercise or rest intervals) BFR (M-exBFR and M-intBFR). Intramuscular metabolic stress, defined as decreases in phosphocreatine and intramuscular pH, was evaluated by 31P magnetic resonance spectroscopy. Rated perceived exertion (RPE) was also assessed. At the end of exercise, total decreases in phosphocreatine and intramuscular pH were similar among L-noBFR, L-intBFR, and L-exBFR and significantly less than those in L-conBFR (p < 0.05). In contrast, changes in these variables in M-intBFR but not in M-exBFR were similar to those in L-conBFR. Nevertheless, RPE was lower in M-intBFR than in both M-exBFR and L-conBFR (p < 0.05). The effect of intermittent BFR during exercise might be insufficient to induce metabolic stress when using a low load. However, effective metabolic stress for muscle adaptation could be obtained by moderate-load resistance exercise with BFR during intervals with less ischemic duration and discomfort.

Background Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients’ peak aerobic capacity. Methods We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF Results The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of − 0.93 (− 1.82 to − 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of − 1.05 (− 1.96 to − 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. Conclusions T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients’ exercise capacity, and the degree of impact is partly dependent on their LV systolic function.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2019-01-26, 資料番号: PA1910027000

Tension-compression fatigue tests were performed on two types of Ni-based superalloy 718 with different microstructures, to which small artificial defects of various shapes and sizes were introduced. Similar tests were also conducted on hydrogen-charged specimens with defects, with a solute hydrogen content ranging from 26.3 to 91.0 mass ppm. In the non-charged specimens in particular, the fatigue strength susceptibility to defects varied significantly according to the type of microstructural morphology, i.e., a smaller grain size made the alloy more vulnerable to defects. The fatigue limit as a small-crack threshold was successfully predicted using the √area parameter model. Depending on the size of defects, the fatigue limit was calculated in relation to three phases: (i) harmless-defect regime, (ii) small-crack regime and (iii) large-crack regime. Such a classification enabled comprehensive fatigue limit evaluation in a wide array of defects, taking into consideration (a) the defect size over a range of small crack and large crack and (b) the characteristics of the matrix represented by grain size and hardness. In addition, the effect of defects and hydrogen on fatigue strength will be comprehensively discussed, based on a series of experimental results.

Accepted: 2018-05-21, 資料番号: SA1180213000

Although there is a growing consensus about the positive relationship between prevention of overweight/obesity and academic performance in children, relevant studies targeting the relationship between underweight and academic performance are scarce. This study aimed to examine the longitudinal relationship of favorable weight change to academic performance in schoolchildren. We analyzed 2-year longitudinal data derived from 197 seventh-grade children aged 12–13 years. Academic performance was assessed using the total grade points of five academic subjects. Body mass index (BMI) was calculated as body weight (kg)/height (m2). A significant interaction effect of baseline BMI and BMI changes over 2 years (B = −0.10, SE B = 0.03, β = −0.40, t = –3.37, p p B = 0.40, SE B = 0.18, β = 0.31, t = 2.20, p = 0.03) and weight loss when baseline BMI = mean + 1 SD (B = −0.26, SE B = 0.13, β = −0.20, t = −1.97, p = 0.05) to total grade points of five school subjects. A split-group validation was performed and robust results of original analyses were detected (i.e., significant interaction effect of baseline BMI and BMI changes over 2 years (group A: B = −0.11, SE B = 0.05, β = −0.47, t = −2.39, p = 0.02; group B: B = −0.14, SE B = 0.05, β = −0.47, t = −2.78, p = 0.007). Favorable changes in weight status, i.e., weight loss in children with overweight/obesity and weight gain in children with mild underweight/underweight, have a positive influence on academic performance in children independent of socioeconomic factors, learning habits, screen time, exercise habits, and cardiorespiratory fitness.

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I–III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=−0.256), but not at rest (r=−0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (

The aim of this study was to determine, using structural equation modeling, the comprehensive relationships of achievement motivation (self-fulfillment achievement motivation [SFAM] and competitive achievement motivation [CAM]), daily behaviors (exercise habits, screen time, and learning duration), body mass index [BMI], and cardiorespiratory fitness [CRF]) with academic performance among schoolchildren. Three hundred twenty-five schoolchildren (172 males and 153 females; 12–13 years old) were recruited. Academic performance was assessed using the total grade points in 8 academic subjects (GP8); CRF using the 20-m shuttle run; and achievement motivation, daily behaviors, and socioeconomic status using questionnaires. Socioeconomic status was included as a control variable. In males, two cascade associations of achievement motivation to GP8 were detected: (1) SFAM → screen time/learning duration → GP8, and (2) CAM → exercise habit → CRF → GP8 (χ 2 = 8.72, p = .19, AGFI = .92). In females, two cascade associations were also detected: (1) SFAM → screen time/learning habit → GP8, and (2) exercise habit → BMI 2 → GP8 (χ 2 = 6.17, p = .41, AGFI = .93). Our results suggest that greater achievement motivation is associated with academic success via various physiological/behavioral factors, and that these associations differ by gender.

This study investigated whether jump training with blood flow restriction (BFR) improves jump performance compared to jump training without BFR under similar exercise intensity in healthy young humans. The participants were twenty healthy males who were assigned to either jump training with BFR (n = 10) or jump training without BFR [control (CON); n = 10] groups. All subjects completed five sets of 10 repetitions with one-minute intervals of half-squat jumps (SJ) at maximal effort, four days a week for four weeks. In the BFR group, circulatory occlusion around both thigh muscles was applied at a pressure of 200 mmHg, and physical characteristics, muscle strength and jump performance were evaluated before and after training. A significant main effect of training period on lean body mass, percentage of body fat and leg circumference in both groups was observed (P < 0.05). For jump training with BFR, only knee flexion strength increased (P < 0.05), while in the CON group, both knee extension and flexion strength increased (P < 0.05). BFR training did not improve SJ or counter-movement jumps (CMJ) (P > 0.05), whereas training without BFR (CON) improved the performance of both jumps (SJ: pre 35.7 ± 5.1 vs. post 38.9 ± 4.1 cm, P = 0.002: CMJ: pre 41.6 ± 3.6 vs. post 44.6 ± 3.8 cm, P < 0.001). These results indicate that jump training with BFR may not be an effective strategy for improving jump performance.

The purpose of this study was to determine, using structural equation modelling (SEM), the direct and indirect influence of daily behaviours (i.e. exercise/learning durations), weight status, and physical fitness on academic performance among seventh-grade schoolchildren, after controlling for socioeconomic status. We analysed cross-sectional data from 274 schoolchildren (159 males and 115 females; 12-13 years old). Academic performance was assessed using the total grade points in eight academic subjects. Physical fitness was evaluated using the total score of eight physical fitness tests and weight status using body mass index. The daily behaviours and socioeconomic status were assessed by the questionnaire. The SEM showed an adequate fit to the data (χ

Aims/Introduction Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle.

Purpose Students who study intensively in one of Japan's ‘cram schools’ and/or spend excess time on electronic devices such as video games are in a sedentary state much of the time, and this may affect their physical fitness. We investigated whether there are relationships among obesity, physical fitness and academic achievement in Japanese students after controlling for socioeconomic and behavioral confounding factors. Methods The data of 315 students (152 females [48%], 163 males [52%]; 12–13 yrs old) were analyzed. Academic achievement was assessed by the total grade points on eight school subjects (GP8). Students with a body mass index at or above the 85th percentile of each gender were classified as the overweight/obese group. Physical fitness was evaluated by the total score on eight fitness tests. Socioeconomic and behavioral confounders including the mother's educational background, household income, cram school utilization and time spent on video games/mobile phones were used as covariates. Results The GP8 of the overweight/obese students was significantly lower than that of the normal weight students (27.2 vs. 29.0 points, respectively). After adjusting for the confounders, the physical fitness score was found to be a significant factor for determinants of GP8 in boys (β = 0.324), but not in girls. The obesity status was a factor for GP8 in the girls (β = − 0.160) but not in the boys. Conclusion These results suggest that physical fitness in boys and obesity status in girls could be important factors not only for health status but also for academic achievement, independent of socioeconomic and behavioral backgrounds.

Aims Exercise capacity is reduced in heart failure (HF) patients, due mostly to skeletal muscle abnormalities including impaired energy metabolism, mitochondrial dysfunction, fiber type transition, and atrophy. Glucagon-like peptide-1 (GLP-1) has been shown to improve exercise capacity in HF patients. We investigated the effects of the administration of a dipeptidyl peptidase (DPP)-4 inhibitor on the exercise capacity and skeletal muscle abnormalities in an HF mouse model after myocardial infarction (MI). Methods and Results MI was created in male C57BL/6J mice by ligating the left coronary artery, and a sham operation was performed in other mice. The mice were then divided into two groups according to the treatment with or without a DPP-4 inhibitor, MK-0626 (1 mg/kg body weight/day) provided in the diet. Four weeks later, the exercise capacity evaluated by treadmill test was revealed to be limited in the MI mice, and it was ameliorated in the MI+MK-0626 group without affecting the infarct size or cardiac function. The citrate synthase activity, mitochondrial oxidative phosphorylation capacity, supercomplex formation and their quantity were reduced in the skeletal muscle from the MI mice, and these decreases were normalized in the MI+MK-0626 group, in association with the improvement of mitochondrial biogenesis. Immunohistochemical staining also revealed that a shift toward the fast-twitch fiber type in the MI mice was also reversed by MK-0626. Favorable effects of MK-0626 were significantly inhibited by treatment of GLP-1 antagonist, Exendin-(9-39) (150 pmol/kg body weight/min, subcutaneous osmotic pumps) in MI+MK-0626 mice. Similarly, exercise capacity and mitochondrial function were significantly improved by treatment of GLP-1 agonist, Exendin-4 (1 nmol/kg/body weight/hour, subcutaneous osmotic pumps). Conclusions A DPP-4 inhibitor may be a novel therapeutic agent against the exercise intolerance seen in HF patients by improving the mitochondrial biogenesis in their skeletal muscle.

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6 J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10 mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress.

The thermal behavior of cryogenic propellant tanks is crucial issue in the operation of cryogenic propulsion systems. Herein, ground experiments were conducted in a 600-mm-diameter cryogenic tank filled with liquid nitrogen. As pre-pressurants, gaseous helium and gaseous nitrogen (of the same species as the liquid), were used to investigate its effect in accordance with actual propulsion systems. The tank was sealed after pre-pressurization to observe the self-pressurization. The evaporation rate and heat flow in the tank were estimated based on pressure and temperature measurements. In addition, the axial liquid temperature distribution was obtained through the liquid draining from the tank bottom, and a thermal stratification model was developed. These results demonstrated that the type of pre-pressurant significantly affected the thermal behavior in the tank. A higher evaporation rate and higher liquid internal energy rise rate with a thicker thermal layer were observed in the helium pre-pressurization case. The lower nitrogen partial pressure in the helium case enhanced the vaporization and growth of the thermal layer. Estimation of the power balance in the tank demonstrated that not only the ullage but also the heat mass of the tank provided heat for the evaporation and thermal layer. The evaporation occurs mainly at the contact point between the tank skin and liquid surface. The nitrogen vapor rises in a thin layer along the tank skin because of buoyancy under nitrogen pre-pressurization; however, buoyancy is lower under helium pre-pressurization, and a radial vapor flow is probably produced from the contact point instead, leading to a higher heat flux to the liquid.

We investigated the effects of age on microvascular responses during reactive hyperemia and arterial stiffness in 13 young (22 ± 1 years), 12 middle-aged (42 ± 5 years), and 15 older (63 ± 2 years) women. During the vascular occlusion test (VOT), forearm tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS). During reperfusion, the area under the curve (AUC) during hyperemia in young women (1123 ± 208% s) was significantly greater than that in middle-aged (771 ± 445% s, P = 0.024) and older women (619 ± 356% s, P = 0.001) with no differences between middle-aged and older women (P = 0.265). Cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness was assessed using four-limb oscillometry. CAVI significantly increased with age (8.1 ± 0.7 in the older group, 6.0 ± 0.8 in the middle-aged group, and 5.8 ± 0.4 in the young group), with significant differences between older women and women in the other groups (P

Background: Brain-derived neurotropic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We investigated whether serum BDNF level was associated with prognosis in patients with heart failure (HF). Methods and Results: We measured the serum BDNF level in 58 patients with HF (59.2 6 13.7 years old, New York Heart Association functional class IeIII) at baseline, and adverse events, including all cardiac deaths and HF rehospitalizations, were recorded during the median follow-up of 20.3 months. In a univariate analysis, serum BDNF levels were significantly associated with peak oxygen capacity (b 5 0.547; P 5 .003), anaerobic threshold (b 5 0.929; P 5 .004), and log minute ventilation/ carbon dioxide production slope (b 5 � 10.15; P 5 .005), but not Patient Health Questionnaire scores (b 5 � 0.099; P 5 .586). A multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 0.41, 95% confidence interval 0.20e0.84; P 5 .003). The receiver operating characteristic curve demonstrated that low levels of BDNF (!17.4 ng/mL) were associated with higher rates of adverse events compared with high levels of BDNF ($17.4 ng/mL; log rank test: P ! .001). Conclusions: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that these levels can be a useful prognostic biomarker. (J Cardiac Fail

In order to improve the accuracy of the expected casualty risk prediction for the destructive re-entry, the related uncertainty factors are identified and the uncertainty quantification approach are proposed. Based on our studies and experience, the identified dominant uncertainty factors are the model accuracy, the attitude stability mode, the shape complexity and shape change, and the initial conditions at the entry start and the break-up. High-fidelity numerical simulations play the important role to model complex multi-disciplinary physics and to cover the wide range of environmental conditions with small numbers of model validation data. The real shape and the deformation effects are initialy modeled by the high-fidelity numerical simulations and finally modeled by the reduced empirical physics-based models. Flight data acquisition also plays important the role to quantify the uncertainties of the attitude stability mode, the break-up altitude, and the temperature distributions and to validate the integrated risk analysis model. Some of the key findings obtained by the high-fidelity simulation are discussed. It is also shown that various types parameter dependencies such as Mach number, wall temperature, surface curvature, and the effect of the turbulent flows on the aerodynamic characteristics and the heat flux distributions should be considered in the empirical models.

Accepted: 2014-07-21, 資料番号: SA1150044000

New findings What is the central question of this study? Does angiotensin II directly induce skeletal muscle abnormalities? What is the main finding and its importance? Angiotensin II induces skeletal muscle abnormalities and reduced exercise capacity. Mitochondrial dysfunction and a decreased number of oxidative fibres are manifest early, while muscle atrophy is seen later. Thus, angiotensin II may play an important role in the skeletal muscle abnormalities observed in a wide variety of diseases. Skeletal muscle abnormalities, such as mitochondrial dysfunction, a decreased percentage of oxidative fibres and atrophy, are the main cause of reduced exercise capacity observed in ageing and various diseases, including heart failure. The renin–angiotensin system, particularly angiotensin II (Ang II), is activated in the skeletal muscle in these conditions. Here, we examined whether Ang II could directly induce these skeletal muscle abnormalities and investigated their time course. Angiotensin II (1000 ng kg−1 min−1) or vehicle was administered to male C57BL/6J mice (10–12 weeks of age) via subcutaneously implanted osmotic minipumps for 1 or 4 weeks. Angiotensin II significantly decreased body and hindlimb skeletal muscle weights compared with vehicle at 4 weeks. In parallel, muscle cross-sectional area was also decreased in the skeletal muscle at 4 weeks. Muscle RING finger-1 and atrogin-1 were significantly increased in the skeletal muscle from mice treated with Ang II. In addition, cleaved caspase-3 and terminal deoxynucleotidyl trasferase-mediated dUTP nick-positive nuclei were significantly increased in mice treated with Ang II at 1 and 4 weeks, respectively. Mitochondrial oxidative enzymes, such as citrate synthase, complex I and complex III activities were significantly decreased in the skeletal muscle from mice treated Ang II at 1 and 4 weeks. NAD(P)H oxidase-derived superoxide production was increased. NADH staining revealed that type I fibres were decreased and type IIb fibres increased in mice treated with Ang II at 1 week. The work and running distance evaluated by a treadmill test were significantly decreased in mice treated with Ang II at 4 weeks. Thus, Ang II could directly induce the abnormalities in skeletal muscle function and structure.

New Findings What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. Abstract We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.

Exercise capacity is lowered in patients with heart failure, which limits their daily activities and also reduces their quality of life. Furthermore, lowered exercise capacity has been well demonstrated to be closely related to the severity and prognosis of heart failure. Skeletal muscle abnormalities including abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, reduction in muscular strength, and muscle atrophy have been shown to play a central role in lowered exercise capacity. The skeletal muscle abnormalities can be classified into the following main types: 1) low endurance due to mitochondrial dysfunction; and 2) low muscle mass and muscle strength due to imbalance of protein synthesis and degradation. The molecular mechanisms of these skeletal muscle abnormalities have been studied mainly using animal models. The current review including our recent study will focus upon the skeletal muscle abnormalities in heart failure.

Accepted: 2019-11-06, 資料番号: SA1190188000