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.

Relationships between locomotive and non-locomotive MVPA and 'ikigai' in older Japanese adults.

Objective: This study aimed to investigate the relationship between physical activity (PA) of moderate to vigorous intensity (MVPA) and ikigai in older Japanese adults. We evaluated the amount of PA using an activity meter equipped with a three-axis accelerometer. The measured activities were classified into locomotive PA and non-locomotive PA to clarify not only the relationship between MVPA and ikigai, but the types of activities that lead to increased ikigai as well. Methods: Participants were 86 community-dwelling older adult Japanese men and women. Measurement items included basic information (age, sex, BMI, and the number of underlying diseases), PA, Self-completed Occupational Performance Index (SOPI), and ikigai (the K-1 Scale). Confounding factors presumed to be related to ikigai were also elicited from previous studies. Associations of ikigai into three groups (high, middle, and low) with PA were analyzed by group comparisons and multivariate analyses. Results: The comparison of PA indices among the high, middle, and low ikigai groups revealed that non-locomotive MVPA is significantly associated with ikigai (p < 0.05). In multiple comparisons, the low ikigai group was significantly and negatively affected by non-locomotive MVPA (p < 0.05) compared to the middle and high ikigai groups. Furthermore, in a multivariate analysis with ikigai as the dependent variable and sex, age, locomotive MVPA, and non-locomotive MVPA as independent variables, only non-locomotive MVPA (p < 0.05) was associated. Discussion: These results suggest that non-locomotive MVPA is effective in enhancing ikigai.

Relationships between physical, cognitive, and social frailty and locomotive and non-locomotive physical activity of moderate to vigorous intensity.

[Purpose] The purpose of this study was to examine the relationships between physical, cognitive, and social frailty and locomotive and non-locomotive physical activity of moderate to vigorous intensity in community-dwelling older adults and to explore effective intervention methods for preventing frailty. [Participants and Methods] Participants were 82 community-dwelling Japanese older males and females. Measurement items included basic information (age, gender, height, weight, body mass index, and the number of underlying diseases), physical activity, and assessment of physical, cognitive, and social frailty. Associations of physical, cognitive, and social frailty with physical activity were analyzed by group comparisons and multivariate analyses. [Results] The comparisons of physical activity indices for each frailty type revealed that physical frailty was associated with the number of steps and locomotive physical activity of moderate to vigorous intensity, whereas cognitive frailty and social frailty were not. Two overlapping types of frailty were associated with locomotive physical activity. When adjusted for age and gender, step counts and locomotive physical activity were each associated with physical frailty. [Conclusion] Future interventions to increase step counts and locomotive physical activity of moderate to vigorous intensity may be effective for preventing physical frailty; however, interventions other than simple physical activity need to be considered for the prevention of cognitive and social frailty.

Interaction Between Sarcopenic Obesity and Nonlocomotive Physical Activity on the Risk of Depressive Symptoms in Community-Dwelling Older Adult Japanese Women.

This study aimed to investigate the interaction between sarcopenic obesity and locomotive and nonlocomotive physical activity (PA) on the risk of depressive symptoms in community-dwelling older Japanese women. Participants were 143 community-dwelling older women aged 64-94 years. PA was measured using a three-axis accelerometer. Participants were classified according to two levels of total, locomotive, and nonlocomotive PA. Depressive symptoms were assessed by a self-administered survey consisting of the 15-item Japanese version of the Geriatric Depression Scale (GDS-15-J). The interaction between sarcopenic obesity groups and total or locomotive PA did not affect GDS-15-J scores. However, the interaction between sarcopenic obesity groups and nonlocomotive PA significantly affected GDS-15-J scores (p < .05). Moreover, sarcopenic obesity in the low PA group had significantly higher GDS-15-J scores compared with sarcopenic obesity in the high PA group (p < .05). We concluded that sarcopenic obesity combined with low nonlocomotive PA may exacerbate depressive symptoms in older women.

Effects of water exercise on body composition and components of metabolic syndrome in older females with sarcopenic obesity.

[Purpose] Very few studies have been conducted on the benefits of water exercise for older adults with sarcopenic obesity. Whether the water exercise intervention is effective for improving sarcopenia and/or obesity remains unclear. This study aimed to investigate the effects of water exercise on body composition and components of metabolic syndrome in older females with sarcopenic obesity. [Participants and Methods] Participants (aged ≥60 years) were divided into a water exercise group and a control group. Water-based strength and endurance exercises were performed three times a week for 12 weeks. Lean soft tissue mass, fat mass, and body fat percentage were measured by dual-energy x-ray absorptiometry. [Results] Two-way analysis of variance revealed significant interactions (time × group) for total body fat percentage and leg body fat percentage. In the exercise group, leg body fat percentage significantly decreased after the intervention, but no significant change was observed in the control group. The components of metabolic syndrome showed no significant interactions in either group (time × group). [Conclusion] No significant changes were observed in the components of metabolic syndrome. However, 12-week water exercise may be effective for reducing fat mass in females with sarcopenic obesity.

Overlap of Physical, Cognitive, and Social Frailty Affects Ikigai in Community-Dwelling Japanese Older Adults.

This study aimed to investigate whether the overlap of physical, cognitive, and social frailty affects Ikigai in community-dwelling Japanese older adults. Participants were 116 community-dwelling older adult Japanese men and women. Associations of physical, cognitive, and social frailty with falls, daily living assessment, and Ikigai were analyzed by group comparisons and multivariate analyses. Physical, cognitive, and social frailty were associated with the risk of falls and Ikigai. An increase in the number of frailty category overlaps was associated with an increased risk of falls and decrease in Ikigai. Multivariate analyses adjusted for confounding factors showed that physical and cognitive frailty were related to Ikigai. In conclusion Two or more overlapping numbers of physical, cognitive, and social frailty had adverse effects on Ikigai in community-dwelling Japanese older adults.

Association between skeletal muscle mass or percent body fat and metabolic syndrome development in Japanese women: A 7-year prospective study.

Previous cross-sectional studies have indicated that low relative appendicular lean mass (ALM) against body weight (divided by body weight, ALM/Wt, or divided by body mass index, ALM/BMI) was negatively associated with metabolic syndrome (MetS). Conversely, previous cross-sectional studies have indicated that the absolute ALM or ALM divided by squared height (ALM/Ht2) were positively associated with MetS. The aim of this longitudinal study was to investigate the association between low absolute or relative skeletal muscle mass, leg muscle power, or percent body fat and the development of MetS in Japanese women in a 7-y prospective study. The study participants included 346 Japanese women aged 26 to 85 years. The participants were divided into low and high groups based on the median values of ALM/Wt, ALM/BMI, ALM/Ht2, absolute ALM, or leg power. The longitudinal relationship between ALM indices or leg power and MetS development was examined using Kaplan-Meier curves and Cox regression models (average follow-up duration 7 years, range 1 to 10 years). During follow-up, 24 participants developed MetS. MetS incidence was higher in the low ALM/Wt group than the high ALM/Wt group even after controlling for age, obesity, waist circumference, family history of diabetes, smoking, and physical activity [adjusted hazard ratio = 5.60 (95% CI; 1.04-30.0)]. In contrast, MetS incidence was lower in the low ALM/Ht2 group than the high ALM/Ht2 group [adjusted hazard ratio = 10.6 (95%CI; 1.27-89.1)]. MetS incidence was not significantly different between the low and high ALM/BMI, absolute ALM, and leg power groups. Both ALM/Ht2 and ALM/Wt were not significant predictive variables for MetS development when fat mass or percent body fat was taken into account in the Cox model. At the very least, the results of this study underscore the importance of body composition measurements in that percent body fat, but not ALM, is associated with MetS development.

Time-dependent relationships between exercise training-induced changes in nitric oxide production and hormone regulation.

Aerobic exercise training (AT) reduces aging-induced deterioration of arterial stiffness and is associated with arterial nitric oxide (NO) production via changes in apelin and adropin as NO-upregulating hormones, and asymmetric dimethylarginine (ADMA) as a NO-downregulating hormone. However, the time-dependent effects of AT on NO production via NO-regulating hormones remain unclear. This study aimed to determine whether AT-induced changes in the time course of NO production via NO-regulating hormones, participate in the AT-induced improvement in central arterial stiffening with advancing age. Methods: Thirty-three healthy Japanese middle-aged and older subjects (67 ± 1 years) were randomly divided into two groups: AT intervention and sedentary controls. Subjects in the training group completed 8-week of AT. Carotid-femoral pulse wave velocity as an index of central arterial stiffness and plasma nitrate/nitrite levels significantly changed from baseline at weeks 6 (P < 0.05) and 8 (P < 0.01). Interestingly, circulating apelin and adropin levels gradually increased during AT intervention and significantly increased from baseline at weeks 4, 6, and 8 (P < 0.01). Additionally, plasma ADMA levels significantly decreased at 8-week AT intervention (P < 0.01). These results suggest that AT-induced changes in the time course of NO production via NO-regulating hormones may participate in AT-induced improvements of central arterial stiffening with advancing age.

Relationship between thigh muscle cross-sectional areas and single leg stand-up test in Japanese older women.

In older adults, the quantitative decline of the quadriceps femoris is associated with the augmentation of difficulty in the execution of a stand-up task. However, it is unclear whether the cross-sectional areas (CSAs) of individual thigh muscles differ between older adults who can stand up from a 40-cm-height chair on a single leg and those who cannot. To investigate this, the present study determined the CSAs of individual mid-thigh muscles in 67 Japanese women aged 60-77 years by using a magnetic resonance imaging method. Participants were asked to stand up from a 40-cm-height chair on a single leg, and those who could and could not stand up without leaning back and maintain a standing posture for 3 seconds on a single leg were allocated into the successful group (SG, n = 40) and unsuccessful group (USG, n = 27), respectively. Only the CSA of the adductors (sum of the adductor longus and adductor magnus) was significantly smaller in USG compared to SG. When CSA was expressed relative to the two-third power of body mass, the values for the four heads of the quadriceps femoris and biceps femoris long head, as well as the adductors, were significantly lower in USG than in SG. The current results indicate that in terms of the value relative to body mass, the reduced CSAs of the adductors and biceps femoris long head, as well as the four heads of the quadriceps femoris, are associated with the failure of attempts to stand up from a 40-cm-height chair on a single leg in older women. This may be due to the anatomical function of the two muscle groups, which contributes to hip extension movement involved in transitioning from a sitting position to a standing position during the stand-up task.

Associations between locomotive and non-locomotive physical activity and physical performance in older community-dwelling females with and without locomotive syndrome: a cross-sectional study.

BACKGROUND: Locomotive syndrome (LS) is a condition of reduced mobility due to a disorder of the locomotive system. Increasing moderate to vigorous physical activity (MVPA) has been recommended to prevent LS. However, to increase daily MVPA is difficult for older people with LS. The MVPA consists of not only locomotive activities such as walking but also non-locomotive activities such as household activities. The aim of this study was to examine the associations between locomotive/non-locomotive MVPA and physical performance in older females with and without LS. METHODS: Participants of this cross-sectional study were 143 older community-dwelling Japanese females. The participants were divided into two groups based on the results of the stand-up test: the normal group (NL) (n = 86) and the LS group (n = 57). Both the locomotive and non-locomotive PA seperately measured with its intensity. The intensity of physical activity (PA) was calculated as METs and classified as sedentary behavior (SB 1-1.5 metabolic equivalent tasks (METs)), low-intensity physical activity (LPA 1.6-2.9 METs), and MVPA (≥ 3 METs). For example, locomotive LPA is slow walking speed of 54 m/min, and locomotive MVPA is walking speed of 67 m/min. While non-locomotive LPA is office work and cooking, non-locomotive MVPA is housecleaning. Physical function was evaluated by handgrip strength, walking speed, and 2-step test. RESULTS: Walking speed, hand-grip strength, 2-step test, daily step counts, and all PA measurements were not significantly different between two groups. In the LS, locomotive MVPA (r = 0.293, p < 0.05) and total MVPA (r = 0.299, p < 0.05) was significantly correlated with walking speed, but not in the NL. CONCLUSIONS: Walking speed was positively correlated with locomotive MVPA and total MVPA in the LS group, but not in NL group. This result suggests that slow walking speed in older people with LS occur in connection with lower locomotive MVPA and total MVPA.

Effect of a 1-year intervention comprising brief counselling sessions and low-dose physical activity recommendations in Japanese adults, and retention of the effect at 2 years: a randomized trial.

BACKGROUND: In an effort to increase people's adherence to active lifestyles, contemporary physical activity (PA) guidelines now include low-dose PA. METHODS: PA was evaluated in 583 participants of the Nutritional and Physical Activity Intervention Study (NEXIS) cohort (30-65 years old); 349 inactive participants (MVPA, 2.7 ± 1.0 MET-h/day) were randomly assigned to the intervention or control groups, and 235 active participants participated in follow-up visits. The intervention aimed to increase MVPA and comprised five brief counseling sessions over 1 year. The 1-year target for the participant was increasing their step-count to 10,000 steps/d or +3000 steps/d, relative to the baseline score. The counseling sessions were designed to stimulate progressive changes in physical behaviors by recommendations promoting small and/or light-intensity bouts of PA. PA was measured at baseline, the end of the intervention, and 1 year after the intervention ended. Additionally, several nutrition, health, and fitness parameters were measured. RESULTS: Participants in the intervention group significantly increased their step-count from 8415 ± 1924 at baseline to 9493 ± 2575 at the end of the 1-year period. During the same period, MVPA significantly increased by 0.9 MET-h. The daily time spent in ≥ 3, ≥ 4 and ≥ 5 MET activities increased by 11, 6, and 3 min, respectively. This increase in PA remained observable 1 year after intervention concluded. The active group maintained higher physical activity levels throughout the two years. The intervention group showed smaller energy intakes at the end of the 2-year period. Significant correlations were noted between the 1-year change in MVPA and the change in resting heart rate (r = - 0.22), and between the 2-year change in MVPA and the change in waist circumference (r = - 0.08) and peak oxygen consumption capacity (r = 0.23) in the intervention group only. CONCLUSIONS: A prolonged and progressive PA intervention promoting small bouts of light-to-moderate PA may be used in healthy, not-optimally-active people to increase PA beyond the strict period of the intervention. Further studies are necessary to understand whether low-dose PA messages can be effective in initiating a progressive increase toward larger amounts of PA. TRIAL REGISTRATION: Clinical Trials.gov, NCT00926744, retrospectively registered.

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.

Relationship between plasma asymmetric dimethylarginine and nitric oxide levels affects aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults.

PURPOSE: Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults. METHODS: Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%-70% peak oxygen uptake [V̇O2peak] for 45 min, 3 days/week). RESULTS: AT significantly increased V̇O2peak (P < 0.05) and decreased carotid ß-stiffness (P < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (P < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid ß-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, P < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid ß-stiffness (r = -0.514, P < 0.01). CONCLUSION: These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.

Adverse effects of the coexistence of locomotive syndrome and sarcopenia on the walking ability and performance of activities of daily living in Japanese elderly females: a cross-sectional study.

[Purpose] The aim of this study was to investigate whether the coexistence of locomotive syndrome and sarcopenia is associated with the risk of fall or performance of activities of daily living in elderly females. [Participants and Methods] We categorized 112 Japanese elderly female participants under three groups: control, locomotive syndrome, and locomotive syndrome and co-existing sarcopenia. We compared the groups based on the mean scores of anthropometric and physical function measurements, the Timed Up and Go test, and the Tokyo Metropolitan Institute of Gerontology Index of Competence to evaluate activities of daily living. [Results] The Timed Up and Go test score significantly differed among the groups. The score of the Timed Up and Go test significantly correlated with scores of the skeletal muscle mass index, skeletal muscle strength grading, and usual gait speed. The total score of the Tokyo Metropolitan Institute of Gerontology Index of Competence significantly decreased in all the groups. [Conclusion] The coexistence of locomotive syndrome and sarcopenia is associated with an increased risk of fall and worsened performance of activities of daily living. Further, the risk of fall is associated with the skeletal muscle mass, skeletal muscle strength, and gait speed. It seems likely that, compared to sarcopenia, locomotive syndrome is more sensitive to lower limb dysfunctions.

Associations among Bone Mineral Density, Physical Activity and Nutritional Intake in Middle-Aged Women with High Levels of Arterial Stiffness: A Pilot Study.

There is little consensus regarding the impacts of physical activity and nutrient intake on bone mineral density (BMD) in subjects with high or low levels of arterial stiffness. This study was performed to investigate whether physical activity and nutrient intake are associated with BMD in middle-aged women with high levels of arterial stiffness. The study population consisted of middle-aged women aged 40-64 years (n = 22). BMD was assessed by dual-energy X-ray absorptiometry. Carotid-femoral pulse wave velocity (cf-PWV) was used as an indicator of arterial stiffness. Subjects were divided into two groups by median cf-PWV. Physical activity in free-living conditions was evaluated using a triaxial accelerometer. Nutrient intake was also measured using the brief-type self-administered diet history questionnaire. In the High-PWV group, BMD showed a significant negative correlation with age. Using a partial correlation model, BMD was associated with the number of steps and unsaturated fatty acid intake in the High-PWV group. These results suggest that BMD in middle-aged women with high levels of arterial stiffness may be associated with both the number of steps and nutritional intake. Recommendations of physical activity and nutritional intake for the prevention of osteopenia should include consideration of arterial stiffness.

Increased serum salusin-α by aerobic exercise training correlates with improvements in arterial stiffness in middle-aged and older adults.

Aging causes arterial stiffening which can be mitigated by increased physical activity. Although low circulating levels of salusin-α are associated with cardiovascular disease, whether salusin-α decreases with aging and whether the reduced arterial stiffening occurring with exercise training is associated with increased serum salusin-α is unknown. Herein we assessed carotid-femoral pulse wave velocity (cfPWV), systolic (SBP) and diastolic (DBP) blood pressures in a cross-sectional study that compared young (20-39-year-old, n=45) versus middle-aged and older (40-80-year-old, n=60) subjects. We also performed an interventional study in which 36 young and 40 middle-aged and older subjects underwent eight weeks of aerobic exercise training. In the cross-sectional study, serum salusin-α levels were lesser in middle-aged and older subjects compared to young individuals and negatively correlated with age, SBP, DBP, or cfPWV. In the interventional study, exercise training increased serum salusin-α in middle-aged and older subjects. Notably, negative correlations were noted between the exercise training-induced changes in serum salusin-α and cfPWV, SBP and DBP. Results indicate that advanced age associates with low circulating salusin-α, the levels of which can be augmented by exercise training. Importantly, increased serum salusin-α with exercise correlates with improvements in arterial stiffness and a reduction in blood pressure.

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.

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.

Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients.

AIMS: The protein myostatin is a member of the transforming growth factor ß superfamily. This is mainly expressed in skeletal muscle and negatively regulates skeletal muscle growth. The present study aimed to elucidate the associations among circulating myostatin level, skeletal muscle mass, and metabolic profiles in Japanese obese patients. METHODS: Japanese obese outpatients (n = 74) were enrolled. We measured clinical parameters, quantified serum myostatin levels, and examined their associations in a cross-sectional manner. RESULTS: Both total skeletal muscle mass and serum myostatin level were higher in males than in females. Among 74 patients, serum myostatin level was positively correlated with skeletal muscle mass and serum immunoreactive insulin (IRI) level [correlation coefficient (r) = 0.294, P = 0.011; r = 0.262, P = 0.024, respectively]. Furthermore, multivariate linear regression analysis revealed that serum myostatin level was positively correlated with IRI after adjusting for gender and skeletal muscle mass (ß-coefficient = 0.230, P = 0.029, R2 = 0.236). CONCLUSIONS: In obese patients, serum myostatin level was elevated in conjunction with an increase in IRI level independent of skeletal muscle mass. This may imply possible novel pathological implications of serum myostatin in muscle mass and metabolism in obese patients with hyperinsulinemia.

Association of sarcopenic obesity predicted by anthropometric measurements and 24-y all-cause mortality in elderly men: The Kuakini Honolulu Heart Program.

OBJECTIVE: The aim of this study was to investigate the association between anthropometric measurements of sarcopenic obesity and all-cause mortality. METHODS: The study included 2309 Japanese-American men ages 71 to 93 y. Mortality data were available for up to 24 y of follow-up. Sarcopenic obesity defined by three patterns of obesity indexes (body mass index [BMI], percent body fat [%BF] and waist circumference [WC]) and skeletal muscle index estimated by anthropometric measurements. RESULTS: Of the 2309 participants, 2210 deaths were reported during the mean follow-up period of 11.7 y. Risk for death was significantly increased with sarcopenia after adjusting for baseline age, lifestyle variables, hypertension, diabetes, and cognitive scores (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.38). Risk for death was significantly decreased with obesity using WC and %BF to define obesity, but not BMI. Risk for death also was significantly increased in the sarcopenia group compared with the optimal group, regardless of which pattern of obesity indexes (BMI, %BF, and WC) was used. Risk for death was significantly increased in sarcopenic obesity defined by WC (HR, 1.19; 95% CI, 1.02-1.38), borderline in the BMI-defined group, and not significant in the %BF-defined group. CONCLUSION: All-cause mortality was increased in men with sarcopenic obesity defined by WC, but not BMI and %BF. Sarcopenia was a stronger predictor of all-cause mortality in this cohort >70 y of age. These results suggest that anthropometric definitions for sarcopenia and sarcopenic obesity are clinically useful as a predictor of all-cause mortality.