Search

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.

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 (R

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.

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. ​

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.

Effective maintenance of a concrete pavement requires precise evaluation of the load transfer efficiency (LTE) at the transverse joint, which is simply calculated from the falling weight deflectometer (FWD) deflections at the loaded and unloaded slabs. In this study, the FWD deflections were simulated with the randomly generated elastic moduli of the pavement layers using the three dimensional finite element method considering the degradation process at a joint, which was categorized into five stages, from completely sound, to having broken dowels and a void underneath the joint. A database of FWD deflections, layer elastic moduli and the associated stage was created from the simulation results. The layer moduli were identified from the measured FWD deflections at a joint by searching the closest calculated FWD deflections to those measured from the database. The results of the analysis not only provide the layer moduli, but also the degradation stage of the joint to help engineers determine the appropriate rehabilitation measures. The method was validated on a 16 year old concrete pavement, on which the FWD measurements were performed three times: just before opening to traffic, after 9 years and 16 years of service. The identified layer moduli were not changed after 16 years of service, and some joints degraded owing to dowel corrosion, broken dowels and the existence of voids underneath the joints. The developed method is able to show the entire picture of the state of the joints in a section and also provide information on which parts of a particular joint have deteriorated.

Chronic

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.

In understanding the relationship between exercise and immunity, the “open window theory” is a well-known theory stating that immediately after high intensity exercise, temporary immunosuppression occurs, which increases the risk of infections such as upper respiratory tract infections. Why does such a phenomenon occur? Does immunosuppression after severe exercise have physiological significance? In this paper, we propose a theory of super homeostasis. In other words, we verify that the open window theory is an important biological reaction when trying to understand the reason why we do exercise, more than it is the indispensable physiological response to the whole body.

The behavioral response of mice to infection is often demonstrated by a reduction in physical activity. Although it is known that single-stranded (ss) RNA, one of the genomes found in viruses, activates to produce type I interferon (IFNs) and pro-inflammatory cytokine via toll-like receptor (TLR) 7, the effect of TLR7 activation on spontaneous wheel-running activity is little known. To determine whether physical activity is regulated by TLR7 activation or not, we measured R-848 (which is a TLR7 agonist) -induced changes in spontaneous wheel-running activity in mice. Male C3H/HeN mice were IV injected with R-848 (0, 1 and 5 mg/kg), and their wheel-running activity was measured. Also, to clarify the effects of R-848-induced IFN-α, tumor necrosis factor (TNF)-α and prostaglandin (PG) E2 on wheel-running behavior, the R-848-injected wheel-running mice were treated with an inhibitor such as a neutralizing antibody specific to IFN-α, pentoxifylline (PTX) and indomethacin (IDM), respectively. It was observed that dose-dependent R-848 treatment reduced wheel-running activity, and the treatment induced an increase in plasma IFN-α, TNF-α, and PGE2 concentrations. However, the wheel-running activity was not attenuated by the anti-IFN-α antibody, PTX and IDM treatments. Our results suggest that the transient reduction in physical activity after R-848 injection is dose dependent, and that these phenomena might occur independently of the behavior caused by R-848-induced IFN-α, TNF-α and PGE2 via TLR7.

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.

In the present study, we determined whether or not exercise-induced high physical activity could be transmitted via altered gut microbiota. We collected cecal material from male C57BL/6N mice for 12 weeks under two conditions: voluntary wheel running (EX) and sedentary condition (SED). After depleting endogenous gut microbiota, cecal microbiota transplantation (CMT) was initiated in the recipient mice by placing cecal contents of either EX or SED mice into the oral cavity directly with the feeding of a high-fat diet (HFD). After a breeding period of 8 weeks, the physical activity test of the HFD (EX-CMT and SED-CMT) mice was examined. Although EX donor mice were attenuated with increasing body mass and body fat, and induced hypertrophy of the heart was compared with SED donor mice, those parameters did not show any difference between EX-CMT and SED-CMT mice. Nevertheless, high physical activity was observed in EX-CMT mice compared to SED-CMT mice (p < 0.01). These results suggest that exercise-induced high physical activity might be transmitted to un-exercised HFD mice via its altered gut microbiota.

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: 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.

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

Introduction: Aerobic exercise training (AT) in type 2 diabetic patients reduces cardiovascular disease (CVD) risks, such as an impairment of NO-derived vasodilation mediated by obese and hyperinsulinemia. Musclin is a muscle-derived myokine and binds to natriuretic peptide receptor-C (NPR-C). Elevation of circulating musclin level deteriorates of insulin resistance. Furthermore, musclin-induced vasocontraction mediated by NPR-C leads to increase in blood pressures. However, the effect of AT on muscle-derived musclin secretion in type 2 diabetes remains unclear. Hypothesis: This study aimed to clarify whether AT-induced attenuations of muscle-derived musclin secretion and arterial NPR-C expression levels are related to reduction of CVD risks in type 2 diabetes rats. Methods: Twenty 20-week-old male type 2 diabetic (OLETF) rats were randomly divided into two groups; 8-week sedentary control and aerobic exercise training (treadmill running for 60min at 25m/min, 5days/week) (n=7 each group) and seven male LETO rats used as healthy sedentary control. After 8 weeks, we measured carotid-femoral pulse wave velocity (cfPWV, an index of arterial stiffness), QUICKI (an index of insulin sensitivity), plasma and muscle musclin levels and GLUT4 translocation levels, arterial NPR-C protein expression. Results: In sedentary diabetic rats, cfPWV, serum insulin and muscle musclin levels, and arterial NPR-C protein expression increased, and QUICKI decreased as compared to healthy sedentary rats (each p Conclusions: These results suggest that attenuation of arterial NPR-C expression and muscle-derived musclin secretion is related to reductions of arterial stiffness and hyperinsulinemia by AT in type 2 diabetic rats.

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.

Although palmitoleic acid (C16:1) is associated with arrhythmias, and increases in an age-dependent matter, the effects of L-carnitine, which is essential for the transport of long-chain fatty acids into the mitochondria, are unclear. It has been postulated that L-carnitine may attenuate palmitate (C16:0)-induced mitochondrial dysfunction and the apoptosis of cardiomyocytes. The aim of this study was to elucidate the activity of L-carnitine in the prevention of the palmitoleic acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoleoyl-CoA-induced mitochondrial respiration was not accelerated by L-carnitine treatment, and this respiration was slightly inhibited by oligomycin, which is an inhibitor of ATP synthase. Despite pretreatment with L-carnitine, the mitochondrial membrane potential decreased and mitochondrial swelling was induced by palmitoleoyl-CoA. In the presence of a combination of L-carnitine and tiron, a free radical scavenger, there was attenuated mitochondrial swelling and cytochrome c release following palmitoleoyl-CoA treatment. We concluded that palmitoleic acid, but not palmitate, induces the cardiac mitochondrial membrane permeability transition despite the presence of L-carnitine.

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.

It remains unclear whether immune response to viral infection is inhibited by severe exercise. We determined whether exhaustive exercise inhibits interferon (IFN)-β and tumor necrosis factor (TNF)-α production after injection of synthetic double-stranded (ds) RNAs, a polyriboinosinic polyribocytidylic acid (poly I:C), as viral infection model. Male C3H/HeN mice, which were divided into exhaustive-exercised and non-exercised groups, were injected with poly I:C (5 mg/kg). Although TNF-α in response to poly I:C was significantly inhibited by exhaustive exercise, IFN-β was no different in both groups. In in-vitro experiments, catecholamines inhibited poly I:C-induced TNF-α, but not IFN-β, production in macrophages. These results suggest that anti-virus cytokine IFN-β in response to poly I:C might be maintained despite severe stressful exercise.