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Chronic Chlorella intake and aerobic exercise training reduce arterial stiffness and increase circulating nitric oxide (NO) levels, which has beneficial effects. This study aimed to clarify the combined aortic NO-mediated effects of chronic Chlorella intake and aerobic exercise training on endothelial vasorelaxation in aged mice. In this study, 38-week-old male senescence-accelerated mouse prone 1 (SAMP1) mice were divided into aged sedentary control (Con), aerobic exercise training (AT; voluntary wheel running for 12 weeks), Chlorella intake (CH; 0.5% Chlorella powder in normal diet), and AT and CH combined (AT+CH) groups. Endothelium-dependent vasorelaxation by addition of acetylcholine to the isolated mouse aortic rings was significantly higher in the AT, CH, and AT+CH groups than in the Con group; a significantly greater effect was seen in the AT+CH group than in the AT and CH groups. Similarly, plasma and arterial nitrite/nitrate levels and arterial endothelial NO synthase phosphorylation were significantly higher in the AT, CH, and AT+CH groups than in the Con group; the AT+CH group had higher values than the AT and CH groups. Thus, chronic Chlorella intake combined with aerobic exercise training had pronounced effects on endothelial vasorelaxation in aged mice via an additive increase in arterial NO production. Novelty: Endothelium-dependent vasorelaxation was improved by Chlorella intake and exercise. Chlorella intake and exercise increased arterial Akt/eNOS/NO signaling. This combination approach further improved vasorelaxation via arterial NO production.

Passive stretching reduces stiffness in the lower limb arteries of the stretched limb. To address this physiological mechanism, we measured the change in shear rate in the posterior tibial artery during a single bout of one-legged passive calf stretching compared with that in the non-stretched leg. The diameter, mean blood velocity, blood flow, and shear rate in the posterior tibial artery were measured using Doppler ultrasound before (baseline), during, and after a one-legged passive intermittent calf stretching procedure (six repetitions of 30-s static stretch with 10-s relaxation) in nine healthy young men. In the posterior tibial artery of the stretched leg, the arterial diameter significantly decreased from baseline during the stretching period (baseline vs. stretching period of the 6th set, 0.19 ± 0.01 vs. 0.18 ± 0.01 cm, P

This study aimed to clarify whether muscle-derived irisin secretion induced by aerobic exercise training is involved in reduction of arterial stiffness via arterial nitric oxide (NO) productivity in obesity. In animal study, 16 Otsuka Long-Evans Tokushima Fatty (OLETF) rats with obesity were randomly divided into 2 groups: sedentary control (OLETF-CON) and 8-week aerobic treadmill training (OLETF-EX) groups. In human study, 15 subjects with obesity completed 8-week aerobic exercise training for 45 min at 60%–70% peak oxygen uptake intensity for 3 days/week. As a result of animal study, carotid-femoral pulse wave velocity (cfPWV) was decreased, and arterial phosphorylation levels of AMP-activated protein kinase (AMPK), protein kinase B (Akt), and endothelial NO synthase (eNOS), circulating levels of nitrite/nitrate (NOx) and irisin, and muscle messenger RNA expression of fibronectin type III domain containing 5 (Fndc5) were increased in the OLETF-EX group compared with OLETF-CON group. In a human study, regular aerobic exercise reduced cfPWV and elevated circulating levels of NOx and irisin. Furthermore, change in circulating irisin levels by regular exercise was positively correlated with circulating NOx levels and was negatively correlated with cfPWV. Thus, aerobic exercise training-induced increase in irisin secretion may be related to reduction of arterial stiffness achieved by NO production via activated arterial AMPK–Akt–eNOS signaling pathway in obesity. Novelty Aerobic exercise training promoted irisin secretion with upregulation of muscle Fndc5 gene expression in rats with obesity. Irisin affected the activation of arterial AMPK–Akt–eNOS signaling by aerobic exercise training. Increased serum irisin level by aerobic exercise training was associated with reduction of arterial stiffness in obese adults.

Androgen hormones are important compounds related to body composition and exercise performance in athletes. The intake of Dioscorea esculenta, known as lesser yam, contains diosgenin and resistance training have been shown to normalize the secretion of androgen hormones. This study aimed to clarify the level of androgen hormone secretion and the effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in athletes. First, in a cross-sectional study, we compared the serum androgen hormone [dehydroepiandrosterone (DHEA), testosterone, and 5α-dihydrotestosterone (DHT)] levels between sprint athletes (n = 15) and non-athletes (n = 15). Second, in an 8-week intervention study, sprint athletes were randomly divided into 2 groups: resistance training with placebo (n = 8) or with Dioscorea esculenta (2,000 mg/day) intake (n = 7). The serum DHEA, free testosterone, and DHT levels were lower in athletes than in non-athletes. Dioscorea esculenta intake combined with resistance training increased the arm fat-free mass, the 1 repetition maximum of deadlift and snatch, and the serum DHEA, free testosterone, and DHT levels, compared with resistance training and placebo intake. The results suggested that Dioscorea esculenta intake combined with resistance training has further effects on muscle hypertrophy and strength in athletes by restoring secretion of androgen hormones.

Introduction Regular aerobic exercise reverses aging-induced deterioration of arterial stiffness via an increased arterial nitric oxide (NO) production. Concurrently, asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by aerobic exercise training. A recent study showed that the NOx/ADMA ratio reflects endothelial function and may be an index of the states of cardiovascular disease. However, whether changes in the NOx/ADMA ratio by aerobic exercise training are associated with a decrease in arterial stiffness in healthy middle-aged and older male and female adults remains unclear. Purpose This study aimed to clarify whether the relationship between plasma ADMA and NOx levels affected aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults. Additionally, we examined whether the effect of AT on circulating ADMA levels differed according to sex. Methods Thirty-one healthy middle-aged and older male and female subjects (male = 13, female = 18, 66.4±1.3 years) participated in the study. The subjects were randomly divided into 2 groups: a training group (n=16 [male = 6 / female = 10], 64.8±2.0 years) and a control group (n=15 [male = 7 / female = 8], 68.1±1.6 years). Subjects in the training group performed the AT program, which consisted of cycling on a leg ergometer at 60–70% of peak oxygen uptake (V(·)O2peak)for 45 min/day, 3 days/week for 8 weeks. Before and after the 8-week aerobic exercise training intervention, V(·)O2peak, plasma ADMA levels and plasma NOx levels were measured in all subjects. Also, carotid β-stiffness as an index of arterial stiffness was determined with ultrasonography. Results Aerobic exercise training significantly increased V(·)O2peak (P Conclusion These results suggest that higher NOx/ADMA ratio affects aerobic exercise training-induced reduction of arterial stiffness, regardless of sex in middle-aged and older adults. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan

Objectives Chlorella is a type of unicellular green algae that contains various nutrients. Habitual exercise and chlorella treatment can improve insulin resistance in obese or diabetic animal models. However, the additive effects of combined chlorella intake and aerobic exercise training remain unclear. The aim of this study was to investigate whether a combination of chlorella intake and aerobic exercise training would produce greater effects on improving glycemic control in rats with type 2 diabetes. Methods Twenty-wk-old male rats with type 2 diabetes (Otsuka Long-Evans Tokushima Fatty [OLETF] rats) were randomly divided into four groups: sedentary control, aerobic exercise training (treadmill running for 1 h, 25m/min, 5 d/wk), chlorella intake (0.5% chlorella powder in normal diet), or combination of aerobic exercise training and chlorella intake for 8 wk (n = 7 per group). Results Chlorella intake and aerobic exercise training significantly decreased fasting blood glucose, insulin levels, and total glucose area under the curve during the oral glucose tolerance test and increased the insulin sensitivity index concomitant with muscle phosphatidylinositol-3 kinase (PI3K) activity, protein kinase B (Akt) phosphorylation, and glucose transporter 4 (GLUT4) translocation levels. Furthermore, a combination of chlorella intake and aerobic exercise training significantly further improved these effects compared with aerobic exercise training or chlorella intake alone. Conclusions These results suggested that chlorella intake combined with aerobic exercise training had more pronounced effects on the improvement of glycemic control via further activation of muscle PI3K/Akt/GLUT4 signaling in rats with type 2 diabetes.

Resistance exercise impairs endothelial function. Therefore, it is of paramount importance to devise an effective strategy for restoring endothelial function after resistance exercise. Herein, we tested the hypothesis that resistance exercise-induced endothelial dysfunction would be restored by low-to-moderate intensity cycling. Seventeen young healthy subjects completed two randomized experimental trials: (a) resistance exercise only trial; and (b) cycling after the resistance exercise trial. Following baseline brachial artery flow-mediated dilation (FMD), subjects performed the resistance exercise. Following the resistance exercise, they were asked to rest in the supine position for the assessments of FMD. Subjects in the resistance exercise only trial maintained this supine position for 60 minutes, whereas those in the other trial cycled for 10 minutes after the resistance exercise trial. Subjects were again asked to rest in the supine position after cycling. Then FMD were repeated at 30 and 60 minutes after the resistance exercise in both trials. In the resistance exercise only trial, the increased blood flow and shear rate were disappeared after 1 hour of resting in the supine position, but were maintained in those in the cycling after the resistance trial due to subsequent cycling. Both trials caused a significant impairment in FMD at 10 minutes after the resistance exercise (P < 0.05). This decline was sustained for 60 minutes in the resistance exercise only trial. However, the impaired FMD was restored in the cycling after the resistance exercise trial. In conclusion, impaired endothelial function after the resistance exercise can be restored with 10 minutes of low-to-moderate intensity cycling.

Background Adropin is a peptide hormone that promotes nitric oxide (NO) production via activation of endothelial NO synthase (eNOS) in endothelial cells. Its circulating levels are reduced with aging and increased with aerobic exercise training (AT). Using a mouse model, we hypothesized that AT restores aging‐associated reductions in arterial and circulating adropin and improves adropin‐induced NO‐dependent vasorelaxation. Further, we hypothesized these findings would be consistent with data obtained in elderly humans. Methods and Results In the animal study, 50‐week‐old SAMP1 male mice that underwent 12 weeks of voluntary wheel running, or kept sedentary, were studied. A separate cohort of 25‐week‐old SAMP1 male mice were used as a mature adult sedentary group. In the human study, 14 healthy elderly subjects completed an 8‐week AT program consisting of 45 minutes of cycling 3 days/week. In mice, we show that advanced age is associated with a decline in arterial and circulating levels of adropin along with deterioration of endothelial function, arterial NO production, and adropin‐induced vasodilation. All these defects were restored by AT. Moreover, AT‐induced increases in arterial adropin were correlated with increases in arterial eNOS phosphorylation and NO production. Consistently with these findings in mice, AT in elderly subjects enhanced circulating adropin levels and these effects were correlated with increases in circulating nitrite/nitrate (NOx) and endothelial function. Conclusions Changes in arterial adropin that occur with age or AT relate to alterations in endothelial function and NO production, supporting the notion that adropin should be considered a therapeutic target for vascular aging. Registration URL: https://www.umin.ac.jp ; Unique identifier: UMIN000035520.

Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle‐derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter‐4 (GLUT‐4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle‐derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT‐4 signaling pathway in rats with type 2 diabetes. Male, 20‐week‐old, Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF‐Con) and chronic resistance exercise (OLETF‐RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long‐Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF‐Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT‐4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF‐RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT‐4/Akt signaling pathway. Moreover, chronic resistance exercise‐induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT‐4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle‐derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes., 8‐week resistance exercise significantly reduced musclin protein levels in the skeletal muscle of rats with type 2 diabetes. Importantly, chronic resistance exercise‐induced reduction of musclin protein levels in the skeletal muscle were significantly associated with activation of muscle Akt phosphorylation and GLUT4 translocation. These results suggest that the chronic resistance exercise‐induced reduction of musclin is involved in the improvement of hyperglycemia and insulin resistance via the activation of the muscle Akt/GLUT4 signaling pathway in rats with type 2 diabetes. ​

[Purpose] Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults. [Methods] Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%-70% peak oxygen uptake [V4O2peak] for 45 min, 3 days/week). [Results] AT significantly increased VO2peak (P < 0.05) and decreased carotid β-stiffness (P < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (P < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, P < 0.05), and the AT-induced increase in NOx/ ADMA ratio was negatively correlated with a decrease in carotid β-stiffness (r = -0.514, P < 0.01). [Conclusion] These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.

Interval exercise has been determined to be more effective than continuous exercise for achieving improvement in the cardiovascular function of individuals suffering from cardiovascular disease. However, whether interval exercise improves the cerebrovascular function remains unclear. As per our hypothesis, interval exercise induces a higher cerebrovascular shear rate (SR) than continuous exercise. In this study, 11 adult men randomly performed continuous exercise for 12 min or work‐equivalent (57.6 kJ/exercise session) interval exercise of semi‐recumbent cycling. The SR in the internal carotid artery (ICA) represents an index of the cerebrovascular SR, which was measured during both the exercises using Doppler ultrasonography. Both the aerobic exercise modes increased the ICA SR. Moreover, the average ICA SR of the interval exercise for the final 4 min of exercise or 2 min of recovery was significantly higher than that for continuous exercise (exercise, 351 ± 75 vs. 330 ± 61/s, p = .038; recovery, 327 ± 86 vs. 290 ± 56/s, p = .014). To our knowledge, this is the first study to show that aerobic interval exercise increased the ICA SR more than equivalent work volume of aerobic continuous exercise. Thus, aerobic interval exercise may be more effective at stimulating the cerebrovasculature, resulting in greater improvements in cerebrovascular function as compared to continuous aerobic exercise in healthy adult men. These findings provide some important information that would help enhance exercise therapy programs for patients with arteriosclerosis, especially in the cerebral circulation., Internal carotid artery image and cerebrovascular parameters during continuous and interval exercise by Doppler ultrasonography.

Funding Acknowledgements Supported by Grants-in-Aid for Scientific Research (#17H02182, #16K13059, M. Iemitsu; #18J01024, S. Fujie) Introduction Aging is well known to elevate risks of cardiovascular diseases. As a mechanism of these increased risks with aging, a reduction of nitric oxide (NO) production via augmented secretion of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis is related. Habitual aerobic exercise has shown to improve secretory unbalance of endothelium-derived regulating factors with aging, such as increase in NO and decrease in ADMA, resulting in the reduction of arterial stiffness. However, the time course of improvement in secretory unbalance of NO and ADMA productions in response to exercise training in middle-aged and older adults remains unclear. Purpose This study aimed to determine the time course of changes in plasma nitrite/nitrate (NOx) and ADMA levels related to exercise-training effects of arterial stiffness in healthy middle-aged and older adults. Methods Thirty-two Japanese healthy middle-aged and older subjects (67 ± 1 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). We evaluated plasma NOx and ADMA concentrations and carotid-femoral pulse wave velocity (cfPWV) as an index of arterial stiffness, measured every 2 weeks for 8-week in the training group. Results cfPWV was gradually declined from baseline to 8-week and significantly decreased from baseline at weeks 6 (P < 0.05) and 8 (P < 0.01). Plasma NOx level was gradually elevated during exercise intervention and significantly increased from baseline at weeks 6 (P < 0.05) and 8 (P < 0.01). Interestingly, plasma ADMA level was significantly decreased at 8-week intervention (P < 0.05). Furthermore, the exercise training-induced reduction in plasma ADMA level was negatively correlated with the change in plasma NOx level before and after the 8-week (r = -0.483, P < 0.05). The exercise training-induced change in plasma ADMA concentration was positively correlated with training-induced change in cfPWV before and after the 8-week (r = 0.633, P < 0.01). Additionally, there was a negative correlation between the changes in plasma NOx level and cfPWV before and after the 8-week (r = -0.642, P < 0.05). Conclusions These results suggest that habitual aerobic exercise can normalize the secretory unbalance of NO and ADMA productions in 6 to 8 weeks, and these balance normalizations may be contributed to the reduction of arterial stiffness in the middle-aged and older adults.

Resistance exercise impairs endothelial function, and this impairment is thought to be mediated by sustained elevation in blood pressure. Herein, we tested the hypothesis that resistance exercise-induced endothelial dysfunction would be prevented by high-intensity resistance exercise with low repetitions. This type of resistance exercise is known to induce temporal elevation in blood pressure due to low repetitions and a long resting period between sets. Thirteen young healthy subjects completed three randomized experimental trials as follows: 1) moderate-intensity exercise with moderate repetitions (moderate-moderate trial), 2) low-intensity exercise with high repetitions (low-high trial), and 3) high-intensity exercise with low repetitions (high-low trial). After baseline brachial artery flow-mediated dilation (FMD) and blood pressure measurements, subjects performed resistance exercise according to the different types of trials. Thereafter, brachial artery FMD and blood pressure measurements were repeated 10, 30, and 60 min after the exercise. Exercise-induced increases in blood flow and shear rate were significantly lower in the high-low trial than in the other two trials ( P < 0.05). Although systolic blood pressures were significantly elevated after exercise in all trials ( P < 0.05), the magnitudes of rise in blood pressure increase were significantly lower in the high-low trial than in the moderate-moderate and low-high trials ( P < 0.05). Moderate-moderate and low-high trials caused a significant impairment in brachial artery FMD ( P < 0.05), which could be prevented through high-intensity resistance exercise with low repetitions ( > 0.05). In conclusion, endothelial function was maintained by conducting high-intensity resistance exercise with low repetitions.NEW & NOTEWORTHY Data from the present study reveal that high-intensity resistance exercise with low repetitions can maintain endothelial function. Thus, this study provides the first evidence that the detrimental vascular effects of resistance exercise are preventable when resistance exercise is performed in high intensity with low repetitions.Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/type-of-resistance-exercise-and-endothelial-function/ (Japanese version: https://ajpheart.podbean.com/e/japanese-language-podcast-type-of-resistance-exercise-and-endothelial-function/ ).

Effects of increase in muscle 5α-dihydrotestosterone (DHT) levels caused by resistance exercise on regulation of mammalian target of rapamycin (mTOR)- and glucose transporter 4 (GLUT4)-signaling pathways in type 2 diabetic rats were assessed. Twenty-week-old type 2 diabetic rats were randomly divided into the resting control, immediately, 1 hour, or 3 hours after resistance exercise, with or without the pretreatment of 5α-reductase inhibitor. Immediately or 1 hour after exercise, levels of 5α-reductase and DHT as well as phosphorylation levels of AMP-activated protein kinase (AMPK), TBC1 domain family member 1 (TBC1D1), and protein kinase B (Akt) in muscle were significantly elevated. Phosphorylation of muscle Akt substrate of 160 kDa (AS160) and translocation levels of GLUT4 at 1 and 3 hours after resistance exercise were significantly elevated. Additionally, resistance exercise significantly activated the phosphorylation of muscle mTOR immediately, and at 1 and 3 hours and of p70 ribosomal S6 kinase (p70S6K) at 1 and 3 hours. However, pretreatment with the 5α-reductase inhibitor significantly attenuated the exercise-induced activation of Akt/mTOR/p70S6K and Akt/AS160/GLUT4 signaling, but did not affect AMPK/TBC1D1/GLUT4 signaling. These findings suggest that resistance exercise-induced increase in muscle DHT synthesis may contribute to activation of Akt/mTOR/p70S6K- and Akt/AS160/GLUT4 signaling pathways in type 2 diabetic rats.

Adiponectin regulates endothelial nitric oxide synthase in endothelial cells, and body fat loss by aerobic exercise training promotes adiponectin secretion. Recently, C1q/tumor necrosis factor-related proteins (CTRPs) have been identified as novel adipokines and are paralogs of adiponectin, but the association between exercise training-induced reduction of arterial stiffness and circulating CTRPs levels remains unclear. This study aimed to clarify whether the reduction of arterial stiffness in middle-aged and older adults is associated with the change in serum levels of CTRPs induced by exercise training. A total of 52 middle-aged and older participants were randomly divided into two groups: a training group ( n = 26) and a sedentary control group ( n = 26). Participants in the training group completed 8 wk of aerobic exercise training (60–70% peak oxygen uptake for 45 min, 3 days/wk). The reduction of percent whole body fat, abdominal visceral fat area, and carotid-femoral pulse-wave velocity (cfPWV) was significantly greater in the training group than in the control group ( P < 0.05). Moreover, the increase in serum adiponectin, CTRP3, and CTRP5 from baseline to 8 wk was significantly higher in the training group compared with the control group ( P < 0.05). Additionally, the training-induced change in cfPWV was negatively correlated with the training-induced change in serum adiponectin, CTRP3, and CTRP5 levels ( r = −0.51, r = −0.48, r = −0.42, respectively, P < 0.05), and increased plasma nitrite/nitrate level by exercise training was correlated only with adiponectin levels ( r = 0.41, P < 0.05). These results suggest that the exercise training-induced increase in serum CTRPs levels may be associated with the reduction of arterial stiffness in middle-aged and older adults.

To clarify whether the relaxation period during stretching affects the degree of elevated shear rate and the degree of reduction of arterial stiffness, we examined relaxation duration to build an adequate stretching protocol. In Experiment 1, the changes in cardiac output, the shear rate in the posterior tibial artery, and blood volume in the calf muscle were measured during recovery (0–60 s) from a single bout of one-legged passive calf stretching in 12 healthy young men. In Experiment 2, the effects of different relaxation periods (5-, 10-, 20-, and 60-s) of passive one-legged intermittent calf stretching (30-s × 6 sets) on the femoral-ankle pulse wave velocity (faPWV) as an index of peripheral arterial stiffness were identified in 17 healthy young men. As a result, the stretched leg’s shear rate significantly increased from 0 to 10th s after stretching. The muscle blood volume in the stretched leg significantly reduced during stretching, and then significantly increased during the recovery period after stretching; however, cardiac output remained unchanged during stretching and recovery. Additionally, the reduction in faPWV from the pre-stretching value in the stretched leg was significantly larger in the protocol with 10-s and 20-s relaxation periods than that in the non-stretched leg, but this did not differ in the 5-s and 60-s relaxation periods. These findings suggest that the relaxation periods of intermittent static stretching that cause a high transient increase in shear rate (via reperfusion after microvascular compression by the stretched calf muscles) are effective to reduce arterial stiffness.

We examined effects of high-intensity training on chemically induced aberrant crypt foci (ACF) in rat colon. We also investigated mechanisms that may underlie the results obtained, with a focus on secreted protein acidic and rich in cysteine (SPARC), which has been proposed as an exercise-related factor of colon cancer prevention.After an administration of 1,2-dimethylhydrazine, F344 rats executed high-intensity intermittent swimming training (HIIST) (twelve 20-s swimming with a weight [16% body weight] with 10-s pauses between the bouts) 5 d·wk for 4 wk. The acute and chronic effects of the HIIST on SPARC were evaluated in rats. We evaluated the in vitro and in vivo effects of 5' AMP-activated protein kinase (AMPK) activator on SPARC in rat serum and epitrochlearis muscle. In human subjects, we determined serum SPARC after exhaustive bicycling consisting of six to seven bouts of exercise at 170% V˙O2max with 10-s rests between the bouts (high-intensity intermittent bicycling [HIIB]). The SPARC mRNA in human vastus lateralis was measured before and after the HIIB for 4 d·wk for 6 wk (HIIB-training [HIIBT]).The numbers of ACF were lower in the HIIST (47 ± 22) compared with the control (122 ± 47) rats (P0.05). SPARC in epitrochlearis and serum after HIIS of the trained rat was higher than that in the control resting rats. In vitro and vivo AMPK stimulation increased mRNA and SPARC protein in rat epitrochlearis, respectively. The human serum SPARC after the HIIB was elevated. SPARC mRNA in human muscle was elevated after the HIIBT.The results demonstrated that HIIST inhibits 1,2-dimethylhydrazine-induced colon ACF development. This effect may be explained by SPARC induction by the exercise intensity-related factor AMPK, potentially explaining the preventive effects of high-intensity intermittent exercise training against colon cancer.

Our previous study demonstrated that a single bout of stretching exercises acutely reduced arterial stiffness. We hypothesized that this acute vascular response is due to regional mechanical stimulation of the peripheral arteries. To test this hypothesis, we examined the effect of a single bout of passive one leg stretching on arterial stiffness, comparing the stretched and the non-stretched leg in the same subject. Twenty-five healthy young men (20.9 ± 0.3 years, 172.5 ± 1.4 cm, 64.1 ± 1.2 kg) volunteered for the study. Subjects underwent a passive calf stretching on one leg (six repetitions of 30-s static stretch with a 10-s recovery). Pulse wave velocity (PWV, an index of arterial stiffness), blood pressure (BP), and heart rate (HR) were measured before and immediately, 15, and 30 min after the stretching. Femoral–ankle PWV (faPWV) in the stretched leg was significantly decreased from baseline (835.0 ± 15.9 cm/s) to immediately (802.9 ± 16.8 cm/s, P

We investigated the associations between the DRD2/ANKK1 genotype (rs1800497, C > T) and both physical activity (PA) level and exercise habit. A total of 648 Japanese men and women aged 26 – 82 years were included in this cross-sectional study. The PA level was evaluated using a triaxial accelerometer. Exercise habits in the past year and in the period from childhood to adolescence were assessed using a questionnaire. There were no significant differences in PA level or exercise habit in the past year among the DRD2/ANKK1 genotypes. On the other hand, there was a significant association between the DRD2/ANKK1 genotype and exercise habit in the period from childhood to adolescence. Regular exercisers (Ex) showed a lower proportion of the CC genotype than non-exercisers (Non-Ex) (P < 0.05). Logistic regression analysis for exercise habit in the period from childhood to adolescence, controlling for gender and age in an additive genetic model, indicated significant associations with increased likelihood of exercisers (Ex) carrying the T allele, OR = 1.38 (95% CI: 1.06 – 1.80, P < 0.05). In conclusion, it was suggested that the DRD2/ANKK1 genotype is associated with exercise habit in the period from childhood to adolescence, but not current PA and exercise habit in the past year.

Age-induced chronic inflammation is prevented by aerobic and resistance exercise training. However, the effects of the mechanism of exercise on chronic inflammation in each tissue remains unclear. The aim of this study was to investigate the effects of resistance and aerobic training on gene expression profiles for macrophage infiltration and polarization (M1/M2 ratio) with chronic inflammation in various tissues of aged model mice. Male 38-week-old SAMP1 (senescence-accelerated prone mouse 1) mice were randomly divided into three groups-sedentary (Aged-Sed-SAMP1), aerobic training (Aged-AT-SAMP1; voluntary running), and resistance training-for 12 weeks (Aged-RT-SAMP1; climbing ladder). Resistance and aerobic exercise training prevented an increase in circulating TNF-α levels (a marker of systemic inflammation) in aged SAMP1 mice, along with decreases in tissue inflammatory cytokine (TNF-α and IL-1β) mRNA expression in the heart, liver, small intestine, brain, aorta, adipose, and skeletal muscle, but it did not change the levels in the lung, spleen, and large intestine. Moreover, resistance and aerobic exercise training attenuated increases in F4/80 mRNA expression (macrophage infiltration), the ratio of CD11c/CD163 mRNA expression (M1/M2 macrophage polarization), and MCP-1 mRNA expression (chemokine: a regulator of chronic inflammation) in the chronic inflamed tissues of aged SAMP1 mice. These results suggested that resistance and aerobic exercise training-induced changes in gene expression for macrophage infiltration and polarization in various tissues might be involved in the prevention of age-related tissue chronic inflammation, and lead to a reduction of the increase in circulating TNF-α levels, as a marker of systemic inflammation, in aged SAMP1 mice.

Introduction Conventionally, as an exercise mode which leads to reduction of arterial stiffness, it is well used that moderate-intensity continuous exercise training (MICT). High-intensity interval training (HIIT), such as HIIT program with a total exercise time of 15–30 min is highly time-effective as an exercise mode for which reduces risks of cardiovascular disease. Recent study showed that even shorter HIIT leads to an effective reduction in arterial stiffness. Therefore, HIIT is an effectively exercise therapy which can use in patients with cardiovascular diseases. Although MICT induces vasodilation by acceleration of nitric oxide (NO) production via upregulating arterial endothelial NO synthase (eNOS)/protein kinase B (Akt) signalling pathway, an underlying mechanism of HIIT effects remains unclear. Purpose This study aimed to clarify the effects of short HIIT on arterial stiffness and arterial NO production in rats. Methods Forty 10-week-old male Sprague-Dawley rats were randomly divided into four groups; CON: 8-week sedentary control, MICT: treadmill running for 60 min at 30m/min, 5 days/wk for 8weeks, HIIT: fourteen 20 sec swimming sessions with a weight equivalent to 14–16% of each body weight and 10 sec pause was allowed between exercise sessions, 4 days/wk for 6 weeks from 12-week-old, and RT: ladder climbing, 8–10sets/day, 3 days/wk for 8 weeks groups (n=10 each group). After training session, we measured aortic pulse wave velocity (aortic PWV) as an index of arterial stiffness and plasma nitrite/nitrate (NOx) concentrations and phosphorylation of eNOS and Akt in the aorta. Results Aortic PWV was significantly reduced in both MICT and HIIT groups as compared to CON and RT groups (P Conclusion These results suggest that HIIT increases NO production via the upregulation of arterial Akt/eNOS signalling pathway, resulting in the reduction of arterial stiffness, despite a reduction in total exercise volume as compared with MICT. Acknowledgement/Funding JSPS KAKENHI (#17H02182 and #16K13059 for M. Iemitsu; #18H06423 for N. Hasegawa)

Our previous study showed that lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-&alpha, production is inhibited by acute exhaustive exercise in mice, leading to transient immunodepression after exercise. Sparassis crispa (SC), an edible mushroom, has immunopotentiative properties. This study aimed to clarify the effects of SC intake on reduced LPS-induced TNF-&alpha, production upon exhaustive exercise in mice. Male C3H/HeN mice were randomly divided into three groups: normal chow intake + resting sedentary, normal chow intake + acute exhaustive treadmill running exercise, and SC intake (chow containing 5% SC powder for 8 weeks) + the exhaustive exercise groups. Each group was injected with LPS immediately after the exhaustive exercise or rest. Plasma and tissue TNF-&alpha, levels were significantly decreased by exhaustive exercise. However, this reduction of the TNF-&alpha, level was partially attenuated in the plasma and small intestine by SC intake. Although levels of TLR4 and MyD88 protein expression were significantly decreased in tissues by exhaustive exercise, the reduction of TLR4 and MyD88 levels in the small intestine was partially attenuated by SC intake. These results suggest that SC intake attenuates exhaustive exercise-induced reduction of TNF-&alpha, production via the retention of TLR4 and MyD88 expression in the small intestine.

Inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) are candidate blood biomarkers of cardiovascular disease (CVD). However, no consensus has been reached on the relationships between aging-induced secretion of cytokines and CVD risk. Complement C1q (C1q) secretion increases with aging, and C1q induces proliferation of vascular smooth muscle cells. Therefore, the secretion of C1q with aging may be a risk factor of CVD and reflect arterial stiffening and blood pressures. This study aimed to clarify whether aging-induced increase in serum C1q, TNF-α, and IL-6 levels are associated with arterial stiffness. One hundred twenty-seven healthy subjects participated in this study. Serum C1q, TNF-α, and IL-6 levels and carotid-femoral pulse wave velocity (cfPWV; arterial stiffness index) in middle-aged and older subjects (≥40 years) were significantly increased as compared with those in young subjects (40 years; P 0.05). The serum C1q, TNF-α, and IL-6 levels positively correlated with cfPWV (P 0.05). Furthermore, C1q level contributed independently to the cfPWV variation after adjustment for 11 confounders. Moreover, serum C1q level is associated with cfPWV regardless of sex, but these relationships with TNF-α or IL-6 differed between sex. Importantly, cfPWV gradually increased from the age of 30 years, with simultaneous increase in circulating C1q level. However, TNF-α and IL-6 levels increased after age 50 years, later than the increase in C1q. These results suggest that serum C1q level may reflect the elevation of arterial stiffness that occurs with advancing age and has a potential as a novel biomarker of arterial stiffness.

Introduction: A physically active lifestyle leads to reduced risks of cardiovascular disease events in the elderly. A level of circulating salusin-α is a novel biomarker of cardiovascular disease and is associated with increased arterial stiffness. Indeed, circulating levels of salusin-α are lower in patients with coronary arterial disease and hypertension compared to healthy subjects. However, it is unknown whether circulating salusin-α levels are decreased with advanced age and whether circulating salusin-α levels are associated with the reduced cardiovascular disease risks by exercise lifestyle. Hypothesis: We assessed the hypothesis that salusin-α is involved to the changes in cardiovascular disease risk by aging or exercise-promoting healthy lifestyle. Methods: In Experiment 1, 105 healthy subjects (20-80 years old) participated in a cross-sectional study. The subjects were divided into 2 groups: young (under 40 years, n=45) versus middle-age and older (over 40 years, n=60). In Experiment 2, 36 young subjects (young aerobic exercise training group; Young-AT: n=27 and control group; Young-Con: n=9) and 40 healthy middle-age and older subjects (middle-age and older aerobic exercise training group; Middle-age and older-AT: n=26 and control group; Middle-age and older-Con: n=14) volunteered to participate. Subjects in AT groups completed eight weeks of habitual aerobic exercise (60-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). We measured serum salusin-α level, carotid-femoral pulse wave velocity (cfPWV), brachial artery systolic (SBP) and diastolic (DBP) blood pressures, common carotid intima-media thickness (ccIMT) and VO2peak. Results: In the cross-sectional study, cfPWV, SBP, DBP and ccIMT were significantly higher and serum salusin-α levels were significantly lower in the middle-age and older adults compared to young adults. Negative correlations were observed between serum salusin-α levels and age (r=–0.698, P Conclusions: Changes in salusin-α levels may be a novel biomarker of the increase in cardiovascular disease risks with age and the decrease in cardiovascular disease risks with exercise lifestyle in healthy middle-age and older adults.

Introduction: Habitual aerobic exercise leads to reduction of arterial wall thickness and arterial stiffness with aging. Recently, C1q has been identified as a novel myokine, and the expression of muscle C1q mRNA increases with aging. Additionally, in vivo and in vitro studies, C1q induces proliferation of vascular smooth muscle cells. However, it remains unclear whether the secretion of myokines, C1q, TNF-alpha and IL-6 are related to the changes in cardiovascular disease risk by aging and regular exercise. PURPOSE: This study aimed to clarify whether serum C1q, TNF-alpha and IL-6 levels are associated with the changes in cardiovascular disease risks with aging and regular aerobic exercise. Methods: In a cross-sectional study, 127 healthy male and female subjects (18-81 years) were enrolled in this study. Subjects were divided into two groups; young ( Results: In the cross-sectional study, serum C1q, TNF-alpha and IL-6 levels, cfPWV and ccIMT were significantly higher in middle-aged and older group as compared with young group (respectively p Conclusion: These results suggest that circulating C1q level may reflect the changes of arterial stiffness and thickness with aging and regular exercise, and the reduction of serum C1q level in response to regular aerobic exercise may contribute to the reduction in cardiovascular disease risks in the elderly.

Habitual stretching exercise increases carotid arterial compliance, and acute stretching exercise increases arterial compliance in patients with myocardial infarction. However, it is not known whether this arterial adaptation is sustained after exercise. The aim of this study was to examine the effect of a single bout of stretching exercise on the time course of systemic, central, and peripheral arterial stiffness in healthy young subjects.Twenty-six healthy young men performed static stretching exercise involving the entire body (trunk, upper limb, and lower limb) for 40 mins. Pulse-wave velocity (PWV; an index of arterial stiffness), blood pressure, and heart rate were measured before and 0, 15, 30, and 60 mins after stretching exercise.Femoral-ankle PWV and brachial-ankle PWV were reduced relative to baseline 15 and 30 mins after acute stretching (P0.05); however, these arterial responses were not sustained for longer periods, and both PWV values returned to the baseline levels within 60 mins. By contrast, carotid-femoral PWV was unchanged.These results suggest that chronic and sufficient repetition of muscle stretch stimulation may result in chronic high arterial compliance, although a single bout of stretch exercise acutely affects arterial compliance.

The accumulation of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) is associated with arterial stiffness in middle-aged and older adults. Habitual aerobic exercise induces the improvement of arterial stiffness with reduction in fat accumulation. However, the relationship between aerobic exercise-induced changes in muscular lipids and arterial stiffness remains unclear. The purpose of this study was to investigate whether habitual aerobic exercise-induced changes in IMCL and EMCL content would lead to an improvement of arterial stiffness. First, in a cross-sectional study, we investigated whether cardiorespiratory fitness level affects the association between IMCL or EMCL content and arterial stiffness in 60 middle-aged and older subjects (61.0±1.3 years). Second, in an intervention study, we examined whether aerobic exercise training-induced changes in IMCL and EMCL content are associated with a reduction in arterial stiffness in 18 middle-aged and older subjects (67.0±1.7 years). In the cross-sectional study, IMCL content was negatively correlated with brachial-ankle pulse wave velocity (baPWV) (r=-0.47, P

Previous studies have shown that acute exercise elevates sex steroid hormone concentrations in rodents and that sprint exercise increases circulating testosterone in healthy young men. However, the effect of different exercise intensities on sex steroid hormone responses at different levels of physical fitness is still unclear. In this study, we compared circulating sex steroid hormone responses at different exercise intensities in athletes and non-athletes. Eight male endurance athletes and 11 non-athletes performed two 15 min sessions of submaximal exercise at 40 and 70% peak oxygen uptake (V(O2peak)), respectively, and exercised at 90% V(O2peak) until exhaustion. Venous blood samples were collected during the last minute of each submaximal exercise session and immediately after exhaustion. Acute exercise at 40, 70 and 90% V(O2peak) induced significant increases in serum dehydroepiandrosterone (DHEA) and free testosterone concentrations in non-athletes. On the contrary, only 90% VO2 peak exercise led to an increase in serum DHEA and free testosterone concentrations in athletes. Serum 5α-dihydrotestosterone concentrations increased with 90% V(O2peak) exercise in both athletes and non-athletes. Additionally, serum estradiol concentrations were significantly increased at moderate and high exercise intensities in both athletes and non-athletes. These results indicate that in endurance athletes, serum sex steroid hormone concentrations, especially serum DHEA and 5α-dihydrotestosterone concentrations, increased only with high-intensity exercise, suggesting that different responses of sex steroid hormone secretion are induced by different exercise intensities in individuals with low and high levels of physical fitness. In athletes, therefore, high-intensity exercise may be required to increase circulating sex steroid hormone concentrations.

High-intensity intermittent exercise training (HIIT) has been proposed as an effective approach for improving both, the aerobic and anaerobic exercise capacity. However, the detailed molecular response of the skeletal muscle to HIIT remains unknown. We examined the effects of the HIIT on the global gene expression in the human skeletal muscle. Eleven young healthy men participated in the study and completed a 6-week HIIT program involving exhaustive 6–7 sets of 20-s cycling periods with 10-s rests. In addition to determining the maximal oxygen uptake ($${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$ V ˙ O 2 max ), maximal accumulated oxygen deficit, and thigh muscle cross-sectional area (CSA), muscle biopsy samples were obtained from the vastus lateralis before and after the training to analyse the skeletal muscle transcriptome. The HIIT program significantly increased the $${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$ V ˙ O 2 max , maximal accumulated oxygen deficit, and thigh muscle CSA. The expression of 79 genes was significantly elevated (fold-change >1.2), and that of 73 genes was significantly reduced (fold-change

Increased complement component 1q (C1q) secretion with aging leads to muscle fibrosis and atrophy whereas resistance training attenuates circulating C1q levels. This study aimed to clarify whether resistance exercise-induced reduction of C1q secretion contributes to the inhibition of fibrosis and atrophy in aged muscles. Young (13-wk-old) and aged (38-wk-old) senescence-accelerated mouse prone 1 mice were randomly assigned to one of 4 groups: a young or aged sedentary control group, or a young or aged resistance training (climbing a ladder 3 d/wk for 12 wk) group. We found that resistance training ameliorated muscle fibrosis and atrophy in aged mice, concomitant with decreased circulating and muscle C1q levels and attenuated activation of muscle Wnt signaling (glycogen synthase kinase β/β-catenin), including β-catenin in satellite (Pax7+/DAPI+) and fibroblast (vimentin+/DAPI+) cells. Furthermore, during muscle regeneration after mice were injured by cardiotoxin injection, we observed a reduction in circulating C1q levels, the inhibition of muscle fibrosis and repair, and decreased in the activation of muscle cytoplasmic and nuclear β-catenin in aged mice from the resistance training group, but these effects were cancelled by a single preadministration of exogenous recombinant C1q. In addition, resistance training attenuated aging-related muscle loss concomitant with decreased expression of both muscle ring-finger protein 1 and muscle atrophy F-box in the muscle. Thus, resistance training-induced changes in circulating C1q levels may contribute to the prevention of muscle fibrosis and atrophy via muscle Wnt signaling in senescent mice.-Horii, N., Uchida, M., Hasegawa, N., Fujie, S., Oyanagi, E., Yano, H., Hashimoto, T., Iemitsu, M. Resistance training prevents muscle fibrosis and atrophy via down-regulation of C1q-induced Wnt signaling in senescent mice.

Aerobic training (AT) and high-intensity intermittent training (HIIT) reduce arterial stiffness, whereas resistance training (RT) induces deterioration of or no change in arterial stiffness. However, the molecular mechanism of these effects of different exercise modes remains unclear. This study aimed to clarify the difference of different exercise effects on endothelial nitric oxide synthase (eNOS) signaling pathway and arterial stiffness in rats and humans.In the animal study, forty 10-wk-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (CON), AT (treadmill running, 60 min at 30 m·min, 5 d·wk for 8 wk), RT (ladder climbing, 8-10 sets per day, 3 d·wk for 8 wk), and HIIT (14 repeats of 20-s swimming session with 10-s pause between sessions, 4 d·wk for 6 wk from 12-wk-old) groups (n = 10 in each group). In the human study, we confirmed the effects of 6-wk HIIT and 8-wk AT interventions on central arterial stiffness and plasma nitrite/nitrate level in untrained healthy young men in randomized controlled trial (HIIT, AT, and CON; n = 7 in each group).In the animal study, the effect on aortic pulse wave velocity (PWV), as an index of central arterial stiffness, after HIIT was the same as the decrease in aortic PWV and increase in arterial eNOS/Akt phosphorylation after AT, which was not changed by RT. A negative correlation between aortic PWV and eNOS phosphorylation was observed (r = -0.38, P0.05). In the human study, HIIT- and AT-induced changes in carotid-femoral PWV (HIIT -115.3 ± 63.4 and AT -157.7 ± 45.7 vs CON 71.3 ± 61.1 m·s, each P0.05) decreased, and plasma nitrite/nitrate level increased compared with those in CON.HIIT may reduce central arterial stiffness via the increase in aortic nitric oxide bioavailability despite it being done in a short time and short term and has the same effects as AT.

Dehydroepiandrosterone (DHEA) is a precursor of sex steroid hormones and is converted to testosterone and estradiol. Normally, androgens and estrogens produced adrenal cortex, testis, and ovary; however, recent studies revealed androgens and estrogens are synthesized by peripheral tissues such as brain, skin, liver, kidney, bone, etc. We found skeletal muscles are also capable of synthesizing androgens and estrogens from DHEA. Circulating DHEA provides substrates required for conversion into potent androgens and estrogens in peripheral tissues. Sex steroid hormone administration has important roles: one is that the enhancement of protein synthesis and anabolism, resulting in muscle growth and increased muscle strength. The other is improvement of hyperglycemia through the activation of glucose signaling pathway in skeletal muscle as well as acceleration of muscle lipid metabolism that increase peroxisome proliferator-activated receptor alpha (PPARα) and PPAR delta (PPARδ). We introduce the effect of DHEA and sex steroid hormones administration on muscle glucose and lipid metabolisms as well as the effect of sex steroid hormone on the muscle hypertrophy.

Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5'-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms.

Sex steroid hormones are secreted mainly by the ovary and testis and regulate diverse physiological processes in target tissues. Recent studies have shown that sex steroidogenesis-related mRNA and protein expressions, such as for 17β-hydroxysteroid dehydrogenase (HSD), 3β-HSD, 5α-reductase and aromatase cytochrome P-450 (P450arom) enzymes, are detected in the skeletal muscle, while testosterone, estradiol, and 5α-dihydrotestosterone (DHT) were locally synthesized in skeletal muscle from dehydroepiandrosterone (DHEA). Moreover, in animal and human studies, the sex steroidogenesis enzymes and sex steroid hormone levels in skeletal muscle are upregulated by acute and chronic exercise stimulation. The enhanced muscle sex steroidgenesis is associated with glycemic control via upregulation of muscle glucose transporter-4 (GLUT-4) signaling in obese and diabetic rats and with muscle mass and strength in older men. Thus, an exercise-induced increase of sex steroid hormone in muscle may positively impact age-related concerns such as life-related diseases and sarcopenia.

This study aimed to develop and cross-validate prediction equations for estimating appendicular skeletal muscle mass (ASM) and to examine the relationship between sarcopenia defined by the prediction equations and risk factors for cardiovascular diseases (CVD) or osteoporosis in Japanese men and women. Subjects were healthy men and women aged 20–90 years, who were randomly allocated to the following two groups: the development group (D group; 257 men, 913 women) and the cross-validation group (V group; 119 men, 112 women). To develop prediction equations, stepwise multiple regression analyses were performed on data obtained from the D group, using ASM measured by dual-energy X-ray absorptiometry (DXA) as a dependent variable and five easily obtainable measures (age, height, weight, waist circumference, and handgrip strength) as independent variables. When the prediction equations for ASM estimation were applied to the V group, a significant correlation was found between DXA-measured ASM and predicted ASM in both men and women (R 2 = 0.81 and R 2 = 0.72). Our prediction equations had higher R 2 values compared to previously developed equations (R 2 = 0.75–0.59 and R 2 = 0.69–0.40) in both men and women. Moreover, sarcopenia defined by predicted ASM was related to risk factors for osteoporosis and CVD, as well as sarcopenia defined by DXA-measured ASM. In this study, novel prediction equations were developed and cross-validated in Japanese men and women. Our analyses validated the clinical significance of these prediction equations and showed that previously reported equations were not applicable in a Japanese population.

Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.

The aim of this study was to compare the effects of low-volume, high-intensity aerobic interval training (HAIT) on maximal oxygen consumption ( $$\dot{V}$$ O2max), left ventricular (LV) mass, and heart rate recovery (HRR) with high-volume, moderate-intensity continuous aerobic training (CAT) in sedentary adults. Twenty-four healthy but sedentary male adults (aged 29.2 ± 7.2 years) participated in an 8-week, 3-day a week, supervised exercise intervention. They were randomly assigned to either HAIT (18 min, 180 kcal per exercise session) or CAT (45 min, 360 kcal). $$\dot{V}$$ O2max, LV mass (3T-MRI), and HRR at 1 min (HRR-1) and 2 min (HRR-2) after maximal exercise were measured pre- and post-intervention. Changes in $$\dot{V}$$ O2max during the 8-week intervention were significant (P

The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20 mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5 ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats.

Physical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24–65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease. Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake ( $$\dot V$$ O2peak) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of $$\dot V$$ O2peak for sex and decade. Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and $$\dot V$$ O2peak were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P

The aim of this study was to compare the effects of time-efficient, low-volume interval exercises on cardiorespiratory capacity and left ventricular (LV) mass with traditional continuous exercise in sedentary adults.Forty-two healthy but sedentary male subjects (age 26.5 ± 6.2 yr) participated in an 8-wk, five times per week, supervised exercise intervention. They were randomly assigned to one of three exercise protocols: sprint interval training (SIT, 5 min, 100 kcal), high-intensity interval aerobic training (HIAT, 13 min, 180 kcal), and continuous aerobic training (CAT, 40 min, 360 kcal). Cardiorespiratory capacity (V˙O2max) and LV mass (3T-MRI) were measured preintervention and postintervention.We observed significant (P0.01) increases in V˙O2max in all three groups, and the effect of the HIAT was the greatest of the three (SIT, 16.7% ± 11.6%; HIAT, 22.5% ± 12.2%; CAT, 10.0% ± 8.9%; P = 0.01). There were significant changes in LV mass, stroke volume (SV), and resting HR in both the SIT (LV mass, 6.5% ± 8.3%; SV, 5.3% ± 8.3%; HR, -7.3% ± 11.1%; all P0.05) and HIAT (LV mass, 8.0% ± 8.3%; SV, 12.1% ± 9.8%; HR, -12.7% ± 12.2%; all P0.01) but not in the CAT (LV mass, 2.5% ± 10.1%; SV, 3.6% ± 6.6%; HR, -2.2% ± 13.3%; all P0.05).Our study revealed that V˙O2max improvement with the HIAT was greater than with the CAT despite the HIAT being performed with a far lower volume and in far less time than the CAT. This suggests that the HIAT has potential as a time-efficient training mode to improve V˙O2max in sedentary adults.