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.

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.

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.

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.

Altered gut microbiota richness in individuals with a history of lateral ankle sprain.

This study aimed to examine differences in the intestinal microbiota diversity in individuals with and without a history of a lateral ankle sprain (LAS). Fifty male college student athletes with (n=32) and without (n=18) a LAS history participated in this study. Faecal samples were collected in the morning after awakening during an off-season, and faecal microbiota were characterized via bacteria 16S rRNA amplicon sequencing. Alpha-diversity metrics and ß-diversity indices were calculated to assess the gut microbiota diversity. The LAS-history group significantly had lower Chao1 (p=0.020) and abundance-based coverage estimators (p=0.035) indices compared to the control group. Gut microbiota composition was not significantly different between athletes with a LAS history and controls (R2 =0.01, p 0.414). Athletes with a history of LASs had significantly higher proportions of Bacteroides Fragilis (p=0.024) and Ruminococcus Gnavus (p=0.021) compared with controls. The gut microbiota of athletes with a LAS history had less richness compared to controls, indicating potential associations between a LAS and the gut microbiota. This study highlights the potential link of a LAS to global health. This study may help raise awareness of strategies to prevent long-term health-related negative consequences in people suffering from LASs.

Aerobic exercise training-induced follistatin-like 1 secretion in the skeletal muscle is related to arterial stiffness via arterial NO production in obese rats.

Follistatin-like 1 (FSTL1), which is mainly secreted from skeletal muscle and myocardium, upregulates protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) phosphorylation in vascular endothelial cells. It is unclear whether skeletal muscle- and myocardium-derived FSTL1 secretion induced by aerobic exercise training is involved in the reduction of arterial stiffness via arterial NO production in obese rats. This study aimed to clarify whether aerobic exercise training-induced FSTL1 secretion in myocardium and skeletal muscle is associated with a reduction in arterial stiffness via arterial Akt-eNOS signaling pathway in obese rats. Sixteen Otsuka Long-Evans Tokushima Fatty (OLETF) obese rats were randomly divided into two groups: sedentary control (OLETF-CON) and eight-week aerobic exercise training (treadmill for 60min at 25m/min, 5days/week, OLETF-AT). Eight Long-Evans Tokushima Otsuka (LETO) rats were used as a healthy sedentary control group. In OLETF-CON, serum FSTL1, arterial Akt and eNOS phosphorylation, and arterial nitrite/nitrate (NOx) levels were significantly lower, and carotid-femoral pulse wave velocity (cfPWV) was significantly greater than those in LETO. These parameters were improved in the OLETF-AT compared to the OLETF-CON. In the OLETF-AT, FSTL1 levels in slow-twitch fiber-rich soleus muscle were significantly greater than those in the OLETF-CON, but not in myocardium, fast-twitch fiber-rich tibialis anterior muscle, and adipose tissue. Serum FSTL1 levels were positively correlated with soleus FSTL1, arterial eNOS phosphorylation, and NOx levels and negatively correlated with cfPWV. Thus, aerobic exercise training-induced FSTL1 secretion in slow-twitch fiber-rich muscles may be associated with a reduction in arterial stiffness via arterial NO production in obese rats.

A pilot study: the relationship between salivary MCP-1 and IgA, and exercise performance in long-distance runners and sprinters.

OBJECTIVE: It remains unclear that the relationship between sprint and/or endurance performance and salivary immunological factors and stress hormones in athletes. The aim of this study was to investigate if salivary immunological factors and stress hormones are related to sprint and endurance performance in sprinters and long-distance runners. Fourteen male sprinters provided 100-m record and 22 male long-distance runners provided 5000-m record. Salivary IgA, MCP-1, interleukin-8, and cortisol levels in sprinters and long-distance runners were measured by ELISA assay. RESULTS: No significant differences were found in all salivary parameters between sprinters and long-distance runners. In long-distance runners, the salivary IgA and MCP-1 concentrations and secretory rate significantly correlated with their personal best 5000-m times (r = 0.534, P = 0.011; r = 0.567, P = 0.006; r = 0.452, P = 0.035, respectively). In sprinters, the salivary IgA concentration, MCP-1 concentration, and MCP-1 secretory rate did not correlate with personal best 100-m sprint times (r = - 0.260, P = 0.369; r = 0.128, P = 0.663; r = 0.122, P = 0.677, respectively). Therefore, the present study is the first to determine that immunological factors such as IgA and MCP1 may be related to endurance performance in long-distance runners.

Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes.

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.

Aerobic Exercise Restores Aging-Associated Reductions in Arterial Adropin Levels and Improves Adropin-Induced Nitric Oxide-Dependent Vasorelaxation.

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.

Effects of combined exercise training and Chlorella intake on vasorelaxation mediated by nitric oxide in aged mice.

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.

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 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.

Aerobic exercise training-induced irisin secretion is associated with the reduction of arterial stiffness via nitric oxide production in adults with obesity.

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.

Sparassis crispa Intake Improves the Reduced Lipopolysaccharide-Induced TNF-α Production That Occurs upon Exhaustive Exercise in Mice.

Our previous study showed that lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α 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-α 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-α levels were significantly decreased by exhaustive exercise. However, this reduction of the TNF-α 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-α production via the retention of TLR4 and MyD88 expression in the small intestine.

Aging-induced elevation in circulating complement C1q level is associated with arterial stiffness.

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.

Effect of combination of chlorella intake and aerobic exercise training on glycemic control in type 2 diabetic rats.

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.

Gene Expression Profiles for Macrophage in Tissues in Response to Different Exercise Training Protocols in Senescence Mice.

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-1ß) 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.

Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men.

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 ([Formula: see text]), 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 [Formula: see text], 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 <0.8) after HIIT. Gene ontology analysis of the up-regulated genes revealed that the significantly enriched categories were "glucose metabolism", "extracellular matrix", "angiogenesis", and "mitochondrial membrane". By providing information about a set of genes in the human skeletal muscle that responds to the HIIT, the study provided insight into the mechanism of skeletal muscle adaptation to HIIT.

Reduction of Real-Time Imaging of M1 Macrophage Chemotaxis toward Damaged Muscle Cells is PI3K-Dependent.

Macrophages migrate and invade into damaged muscle rapidly and are important for muscle repair and subsequent regeneration. The exact cellular and biological events that cause macrophage migration toward injured muscle are not completely understood. In this study, the effect of macrophage differentiation on the chemotactic capability to invade local damaged muscle was investigated using an in vitro model of muscle injury. We used C2C12 cell myoblasts and J774 cell macrophages, and the "killed-C2C12" cells were combined with live C2C12 cells as a partially damaged muscle model. The cultured J774 cells, with or without lipopolysaccharide (LPS), were treated with Ly294002 (Ly), which is an inhibitor of phosphoinositide 3-kinase (PI3K). In order to evaluate the polarization effect of LPS stimulation on J774 cells, expression of cell surface Toll-like receptor 4 (TLR4), CD11c and CCR2, and expression of F-actin intensity, were analyzed by flow cytometry. The real-time horizontal chemotaxis assay of J774 cells was tested using the TAXIScan device. The expressions of TLR4, CD11c, and F-actin intensity in LPS-treated cells were significantly higher than those in Ctrl cells. In LPS-treated cells, the chemotactic activity toward damaged muscle cells completely disappeared. Moreover, the reduced chemotaxis depended far more on directionality than velocity. However, Ly treatment reversed the reduced chemotactic activity of the LPS-treated cells. In addition, cell-adhesion and F-actin intensity, but not CCR2 expression, in LPS-treated cells, was significantly reduced by Ly treatment. Taken together, our results suggest that the PI3K/Akt activation state drives migration behavior towards damaged muscle cells.

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.