PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.

Effects of different exercise intensities or durations on salivary IgA secretion.

PURPOSE: This study aimed to examine changes in salivary immunoglobulin A (s-IgA) secretion at different intensities or durations of acute exercise. METHODS: Twelve healthy untrained young males were included in randomized crossover trials in Experiment 1 (cycling exercise for 30 min at a work rate equivalent to 35%, 55%, and 75% maximal oxygen uptake [ V ˙ O2max]) and Experiment 2 (cycling exercise at 55% V ˙ O2max intensity for 30, 60, and 90 min). Saliva samples were collected at baseline, immediately after, and 60 min after each exercise. RESULTS: Experiment 1: The percentage change in the s-IgA secretion rate in the 75% V ˙ O2max trial was significantly lower than that in the 55% V ˙ O2max trial immediately after exercise (- 45.7%). The percentage change in the salivary concentration of cortisol, an s-IgA regulating factor, immediately after exercise significantly increased compared to that at baseline in the 75% V ˙ O2max trial (+ 107.6%). A significant negative correlation was observed between the percentage changes in saliva flow rate and salivary cortisol concentration (r = - 0.52, P < 0.01). Experiment 2: The percentage change in the s-IgA secretion rate in the 90-min trial was significantly lower than that in the 30-min trial immediately after exercise (-37.0%). However, the percentage change in salivary cortisol concentration remained the same. CONCLUSION: Our findings suggest that a reduction in s-IgA secretion is induced by exercise intensity of greater than or equal to 75% V ˙ O2max for 30 min or exercise duration of greater than or equal to 90 min at 55% V ˙ O2max in healthy untrained young men.

Aerobic exercise training-induced alteration of gut microbiota composition affects endurance capacity.

This study aimed to clarify whether aerobic exercise training-induced alterations in the gut microbiota affect physiological adaptation with endurance exercise capacity. In study 1, ICR mice were randomly divided into three groups: vehicle intake + sedentary (V+S), vehicle intake + exercise training (V+Ex) and antibiotic intake + exercise training (AB+Ex). In the exercise training groups, treadmill running was performed for 8 weeks. During the exercise training intervention, the antibiotic-intake group freely drank water containing antibiotics. In study 2, ICR mice were randomly divided into three groups: Sham, transplantation of caecum microbiota from sedentary mice (Sed-CMT) and exercise training mice (Ex-CMT). In study 1, the treadmill running time to exhaustion, an index of maximal aerobic capacity, after aerobic exercise training in the V+Ex group was significantly longer than that in the V+S and AB+Ex groups. Gastrocnemius muscle citrate synthase (CS) activity and PGC-1α protein levels in the V+Ex group were significantly higher than in the V+S and AB+Ex groups. The bacterial Erysipelotrichaceae and Alcaligenaceae families were positively correlated with treadmill running time to exhaustion. In study 2, the treadmill running time to exhaustion after transplantation was significantly higher in the Ex-CMT group than in the Sham and Sed-CMT groups. Furthermore, CS activity and PGC-1α protein levels in the gastrocnemius muscle were significantly higher in the Ex-CMT group than in the Sham and Sed-CMT groups. Thus, gut microbiota altered by aerobic exercise training may be involved in the augmentation of endurance capacity and muscle mitochondrial energy metabolism. KEY POINTS: Aerobic exercise training changes gut microbiota composition, and the Erysipelotrichaceae and Alcaligenaceae families were among the altered gut bacteria. The gut microbiota was associated with endurance performance and metabolic regulator levels in skeletal muscle after aerobic exercise training. Continuous antibiotic treatment attenuated the increase in endurance performance, citrate synthase activity and PGC-1α levels in skeletal muscle induced by aerobic exercise training. Gut microbiota transplantation from exercise-trained mice improved endurance performance and metabolic regulator levels in recipient skeletal muscle, despite the absence of aerobic exercise training.

Relationships between circulating irisin levels, cardiorespiratory fitness, and cardiometabolic risk: a cross-sectional study in Japanese adults.

High cardiorespiratory fitness levels achieved through regular aerobic exercise are associated with reduced cardiometabolic risk. The exercise-induced myokine irisin possibly mediates these associations, but these relationships are unclear. This study aimed to clarify the relationships between circulating irisin levels, cardiorespiratory fitness levels, and cardiometabolic risk factors adjusted for sex and age. This cross-sectional study included 328 Japanese participants aged between 18 and 88 yr. We measured serum irisin levels and peak oxygen uptake (V̇o2peak) as cardiorespiratory fitness indicators, and body fat percentage, blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), high-density lipoprotein (HDL) cholesterol, and triglycerides as cardiometabolic risk factors. Cardiometabolic risk scores were calculated from the z-scores of the cardiometabolic risk factors. Quintiles based on V̇o2peak or irisin values, categorized by sex, showed a gradual increase in HDL cholesterol and a gradual decrease in other cardiometabolic risk factors with an increase in cardiorespiratory fitness levels or irisin. Serum irisin levels were negatively correlated with body fat percentage, blood pressure, fasting blood glucose, HbA1c, triglyceride levels, and cardiometabolic risk score and positively correlated with HDL cholesterol levels and V̇o2peak in both sexes and young, and middle-aged and older adults. The same relationship was observed in all participants after adjusting for sex and age. These results suggest that circulating irisin levels may be involved in the association between cardiorespiratory fitness and cardiometabolic risk factors, regardless of sex and age.NEW & NOTEWORTHY Circulating irisin levels gradually increased, and cardiometabolic risks gradually decreased with increasing cardiorespiratory fitness levels. The fitness levels required to increase irisin levels were moderate for young adults and lower than moderate for middle-aged and older adults. Moreover, circulating irisin levels are correlated with a reduction in cardiometabolic risk and an increase in cardiorespiratory fitness. These data suggest that circulating irisin levels are involved in the association between cardiorespiratory fitness and cardiometabolic risk.

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes.

Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D are associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness, 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase, and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Lastly, we demonstrated that in vivo treatment of db/db mice with adropin for 4 wk reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelium-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.NEW & NOTEWORTHY Arterial stiffening, a characteristic feature of obesity and type 2 diabetes (T2D), contributes to the development and progression of cardiovascular diseases. Herein we establish that adropin is decreased in obese and T2D models and furthermore provide evidence that reduced adropin may directly contribute to arterial stiffening. Collectively, findings from this work support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

Resistance exercise-induced increase in muscle 5α-dihydrotestosterone contributes to the activation of muscle Akt/mTOR/p70S6K- and Akt/AS160/GLUT4-signaling pathways in type 2 diabetic rats.

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.

Acute effect of passive one-legged intermittent static stretching on regional blood flow in young men.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.05) without any change in shear rate and mean blood velocity. In contrast, during the relaxation period, the mean blood velocity (baseline vs. relaxation period of the 5th set, 2.98 ± 0.54 vs. 6.25 ± 1.48 cm/s) increased, and consequently, the shear rate (baseline vs. relaxation period of the 5th set, 66.75 ± 15.39 vs. 122.85 ± 29.40 s-1) increased (each P < 0.01); however, there was no change in arterial diameter. In contrast, these values in the non-stretched leg were unchanged at all-time points. CONCLUSIONS: The stretching procedure increased the shear rate in the peripheral artery of the stretched leg during the relaxation period. This finding indicates that the local hemodynamic response (possibly through endothelial function), resulting from an increase in shear stress, may contribute to stretching-induced attenuation of local arterial stiffness.

Effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in sprint athletes.

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.

Resistance training prevents muscle fibrosis and atrophy via down-regulation of C1q-induced Wnt signaling in senescent mice.

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 ß/ß-catenin), including ß-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 ß-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 exercise training-induced changes in serum C1q/TNF-related protein levels are associated with reduced arterial stiffness in middle-aged and older adults.

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.

High-intensity intermittent exercise training with chlorella intake accelerates exercise performance and muscle glycolytic and oxidative capacity in rats.

The purpose of this study was to investigate the effect of chronic chlorella intake alone or in combination with high-intensity intermittent exercise (HIIE) training on exercise performance and muscle glycolytic and oxidative metabolism in rats. Forty male Sprague-Dawley rats were randomly assigned to the four groups: sedentary control, chlorella intake (0.5% chlorella powder in normal feed), HIIE training, and combination of HIIE training and chlorella intake for 6 wk (n = 10 each group). HIIE training comprised 14 repeats of a 20-s swimming session with a 10-s pause between sessions, while bearing a weight equivalent to 16% of body weight, 4 days/week. Exercise performance was tested after the interventions by measuring the maximal number of HIIE sessions that could be completed. Chlorella intake and HIIE training significantly increased the maximal number of HIIE sessions and enhanced the expression of monocarboxylate transporter (MCT)1, MCT4, and peroxisome proliferator-activated receptor γ coactivator-1α concomitantly with the activities of lactate dehydrogenase (LDH), phosphofructokinase, citrate synthase (CS), and cytochrome-c oxidase (COX) in the red region of the gastrocnemius muscle. Furthermore, the combination further augmented the increased exercise performance and the enhanced expressions and activities. By contrast, in the white region of the muscle, MCT1 expression and LDH, CS, and COX activities did not change. These results showed that compared with only chlorella intake and only HIIE training, chlorella intake combined with HIIE training has a more pronounced effect on exercise performance and muscle glycolytic and oxidative metabolism, in particular, lactate metabolism.

Acute effect of stretching one leg on regional arterial stiffness in young men.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.01) and 15 min (810.5 ± 16.0 cm/s, P < 0.01) after the stretching, despite no changes in systolic and diastolic BP, or HR. However, faPWV in the non-stretched leg was not significantly altered at any time. Brachial-ankle PWV (baPWV) also showed similar responses with faPWV, but this response was not significant. Additionally, the passive stretching did not alter carotid-femoral PWV (cfPWV). CONCLUSIONS: These results suggest that mechanical stimulation to peripheral arteries as induced by static passive stretch may modulate arterial wall properties directly, rather than resulting in a systemic effect.

Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults.

Aging-induced arterial stiffening is reduced by aerobic exercise training, and elevated production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases with age. However, the effect of habitual aerobic exercise on circulating adropin levels in healthy middle-aged and older adults remains unclear. We sought to determine whether serum adropin level is associated with exercise training-induced changes in arterial stiffness. First, in a cross-sectional study, we investigated the association between serum adropin level and both arterial stiffness and cardiorespiratory fitness in 80 healthy middle-aged and older subjects (65.6 ± 0.9 yr). Second, in an intervention study, we examined the effects of 8-wk aerobic exercise training on serum adropin level and arterial stiffness in 40 healthy middle-aged and older subjects (67.3 ± 1.0 yr) divided into two groups: aerobic exercise training and sedentary controls. In the cross-sectional study, serum adropin level was negatively correlated with carotid ß-stiffness (r = -0.437, P < 0.001) and positively correlated with plasma NOx level (r = 0.493, P < 0.001) and cardiorespiratory fitness (r = 0.457, P < 0.001). Serum adropin levels were elevated after the 8-wk aerobic exercise training intervention, and training-induced changes in serum adropin level were correlated with training-induced changes in carotid ß-stiffness (r = -0.399, P < 0.05) and plasma NOx level (r = 0.623, P < 0.001). Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness.

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.

PURPOSE: ß3-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. METHOD: Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake (V̇O(2peak)) 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 V̇O(2peak) for sex and decade. RESULTS: Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and V̇O(2peak) 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 < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects. CONCLUSION: Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.

Effect of resistance training and chicken meat on muscle strength and mass and the gut microbiome of older women: A randomized controlled trial.

This study investigated the effects of white meat, such as chicken, intake combined with resistance training on muscle mass and strength in the elderly women, and whether the underlying mechanism involves changes in the gut microbiota. Ninety-three volunteers (age 59-79 years) were randomly allocated to sedentary control with placebo (Sed + PL) or chicken meat (Sed + HP) and resistance training with placebo (RT + PL) or chicken meat (RT + HP). Resistance training sessions were performed 3 d/week for 12 weeks using leg extensions and curls. Boiled chicken meat (110 g, containing 22.5 g protein) was ingested 3 d/week for 12 weeks. Maximal muscle strength and whole-body lean mass increased significantly in the RT + PL group compared to the Sed + HP group, and the RT + HP group showed a significantly greater increase than the Sed + HP and RT + PL groups. Additionally, the gut microbiota composition did not change before or after the interventions in any of the four groups. Moreover, the individual comparison of gut bacteria using false discovery rate-based statistical analysis showed no alterations before or after the interventions in the four groups. Resistance training combined with chicken meat intake may effective have increased muscle mass and strength without drastically modifying the gut microbiota composition in elderly women.

Higher cardiorespiratory fitness attenuates arterial stiffening associated with the Ala54Thr polymorphism in FABP2.

Fatty acid binding protein 2 (FABP2) Ala54Thr polymorphism is a candidate gene associated with the risk of cardiovascular disease. Habitual exercise brings higher cardiorespiratory fitness and results in the improvement of cardiovascular disease risk. However, the effect of cardiorespiratory fitness level and FABP2 Ala54Thr polymorphism on the risk of cardiovascular diseases remains unclear. In the present study, a cross-sectional investigation of 837 Japanese men and women was performed to clarify the effects of cardiorespiratory fitness on the relationship between risk of cardiovascular disease and FABP2 Ala54Thr gene polymorphism. The study subjects were divided into high-cardiorespiratory fitness (High-Fit) and low-cardiorespiratory fitness (Low-Fit) groups based on the median value of peak oxygen uptake in each sex and decade. The FABP2 Ala54Thr polymorphism did not significantly affect carotid ß-stiffness or blood pressure. In the Low-Fit group, carotid ß-stiffness, systolic blood pressure, and diastolic blood pressure were higher for individuals with the Ala/Ala genotype compared with those with the Ala/Thr or Thr/Thr genotype, whereas no differences were observed in the High-Fit group. Additionally, serum triglyceride and plasma glucose levels were lower and serum high-density lipoprotein cholesterol levels were higher in the High-Fit group compared with the Low-Fit group; the FABP2 Ala54Thr polymorphism did not significantly affect these parameters. These results suggest that the higher cardiorespiratory fitness may attenuate the changes in central arterial stiffness and blood pressure that are associated with the FABP2 genotype.

Effect of acute high-intensity intermittent exercise on serum brain-derived neurotrophic factor concentrations.

BACKGROUND: This study aimed to examine changes in serum brain-derived neurotrophic factor (BDNF) concentrations after exhaustive high-intensity intermittent exercise (HIIE) and non-exhaustive HIIE, and to compare the two conditions. METHODS: Eight healthy male college students (age: 22±1 year) participated in exhaustive (sets: 6-7) and non-exhaustive (sets: 5) HIIE. In both conditions, participants repeated sets of 20 seconds of exercise at 170% V̇O2max with 10 seconds of rest between sets. Serum BDNF was measured 8 times in each condition: 30 minutes after resting, 10 minutes after sitting, immediately after HIIE, and 5, 10, 30, 60, and 90 minutes after main exercise. Changes in serum BDNF concentrations over time and between measurement points in both conditions were measured using a two-way repeated measures ANOVA. RESULTS: Serum BDNF concentrations were measured, revealing significant interaction between two factors (conditions and measurement points) (F=3.482, P=0.027). In the exhaustive HIIE, there were significant increases at 5 minutes (P<0.01) and 10 minutes (P<0.01) after exercise compared to after resting. In the non-exhaustive HIIE, there was a significant increase immediately after (P<0.01) and 5 minutes after (P<0.01) exercise compared to resting. Comparison of the serum BDNF concentrations at each measurement point showed a significant difference at 10 minutes after exercise, with significantly higher values for the exhaustive HIIE condition (P<0.01, r=0.60). CONCLUSIONS: Exhaustive and non-exhaustive HIIE are time-efficient exercises that increase serum BDNF concentrations in healthy adults.

Dioscorea esculenta Intake with Resistance Training Improves Muscle Quantity and Quality in Healthy Middle-Aged and Older Adults: A Randomized Controlled Trial.

Resistance training and Dioscorea esculenta intake have a positive effect on muscle. Therefore, we aimed to determine whether 12-week Dioscorea esculenta intake combined with resistance exercise more effectively improves muscle quantity, quality, and cardiometabolic parameters in healthy middle-aged and older adults. This study is a double-blind trial with 66 volunteers (21 males/45 females; age 53 ± 5 years; body weight 61 ± 11 kg; BMI 24 ± 4 kg) who were randomly divided into four groups: sedentary-control with placebo (Sed and PL) or Dioscorea (Sed and Dio) and resistance training with placebo (RT and PL) or Dioscorea (RT and Dio). Resistance training sessions using elastic bands were performed 3 days/week for a 12-week period. Dioscorea esculenta tablets were ingested at 2000 mg/day once per day. The RT and Dio group showed greater improvements in the femoris muscle's thickness, echo intensity for the rectus femoris (index of muscle quality), and the five times sit-to-stand test compared to that of the Sed and PL group; the echo intensity in the RT and Dio group further improved compared to those in the Sed and Dio, and RT and PL groups (p < 0.05). The circulating levels of C1q (a potential biomarker of muscle fibrosis) in the RT and Dio group were significantly lower than those in the Sed and PL, and Sed and Dio groups (p < 0.05). Chronic Dioscorea esculenta intake combined with low-intensity resistance exercise may more effectively improve muscle quantity and quality indices in healthy middle-aged and older adults.

Effect of Exogenous Acute ß-Hydroxybutyrate Administration on Different Modalities of Exercise Performance in Healthy Rats.

PURPOSE: A ketone body (ß-hydroxybutyrate [ß-HB]) is used as an energy source in the peripheral tissues. However, the effects of acute ß-HB supplementation on different modalities of exercise performance remain unclear. This study aimed to assess the effects of acute ß-HB administration on the exercise performance of rats. METHODS: In study 1, Sprague-Dawley rats were randomly divided into six groups: endurance exercise (EE + PL and EE + KE), resistance exercise (RE + PL and RE + KE), and high-intensity intermittent exercise (HIIE + PL and HIIE + KE) with placebo (PL) or ß-HB salt (KE) administration. In study 2, metabolome analysis using capillary electrophoresis mass spectrometry was performed to profile the effects of ß-HB salt administration on HIIE-induced metabolic responses in the skeletal and heart muscles. RESULTS: The maximal carrying capacity (rest for 3 min after each ladder climb, while carrying heavy weights until the rats could not climb) in the RE + KE group was higher than that in the RE + PL group. The maximum number of HIIE sessions (a 20-s swimming session with a 10-s rest between sessions, while bearing a weight equivalent to 16% of body weight) in the HIIE + KE group was higher than that in the HIIE + PL group. However, there was no significant difference in the time to exhaustion at 30 m·min -1 between the EE + PL and the EE + KE groups. Metabolome analysis showed that the overall tricarboxylic acid cycle and creatine phosphate levels in the skeletal muscle were higher in the HIIE + KE group than those in the HIIE + PL group. CONCLUSIONS: These results indicate that acute ß-HB salt administration may accelerate HIIE and RE performance, and the changes in metabolic responses in the skeletal muscle after ß-HB salt administration may be involved in the enhancement of HIIE performance.

Prior beetroot juice ingestion offsets endothelial dysfunction following prolonged sitting.

Nutritional strategies to prevent endothelial dysfunction following prolonged sitting remain largely unknown. Given that beetroot juice (BRJ) ingestion enhances nitric oxide (NO) bioavailability, we aimed to evaluate whether prior BRJ ingestion would prevent sitting-induced endothelial dysfunction in the leg. Eleven healthy young males (n = 7) and females (n = 4) underwent two experimental trials of prolonged sitting with prior: 1) placebo (PL) ingestion (PL trial) and 2) BRJ ingestion (BRJ trial). All subjects ingested 140 mL of PL or BRJ (∼0.0055 or ∼12.8 mmol of nitrate, respectively) immediately before 3 h of sitting. Pre- and post-sitting measurements of popliteal artery flow-mediated dilation (FMD) and blood pressure, and blood collection were undertaken. During the sitting period, an hourly assessment of popliteal artery diameter and blood velocity, blood pressure, and blood collection were performed. Popliteal artery blood flow and shear rate were significantly and similarly reduced during the sitting period in both trials (P < 0.001). Plasma nitrate and NOx (total nitrite and nitrate) concentrations were significantly increased relative to baseline in the only BRJ trial, and the overall concentrations were significantly higher in the BRJ trial (P < 0.001). Popliteal artery FMD was significantly reduced after the sitting period in the PL trial (P < 0.05), whereas no reduction was observed in the BRJ trial. Therefore, prior BRJ ingestion would prevent sitting-induced leg endothelial dysfunction via enhancing NO bioavailability.NEW & NOTEWORTHY The present study elucidates that beetroot juice ingestion before prolonged sitting offsets sitting-induced leg endothelial dysfunction. Data from the present study provides novel physiological information that enhancing NO bioavailability by dietary nitrate supplementation is an effective tool for prevention of the detrimental vascular effects of prolonged sitting.