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.

Effect of mastication evaluation and intervention on body composition and biochemical indices in female patients with obesity: a randomized controlled trial.

BACKGROUND: A limited number of studies have evaluated the masticatory indices of individuals with obesity who only chew their food a few times and for shorter duration or who were provided with an instructional intervention. This study aimed to examine the effects of a 6-month instructional mastication intervention on the body composition and biochemical indices in female patients with obesity. METHODS: Female patients with obesity were randomly classified into a conventional treatment group (CTG; 12 individuals), which only received normal nutritional and exercise guidance, and a mastication intervention group (MIG; 16 individuals), which received an additional mastication guidance. The MIG received guidance on foods requiring increased number of chews and chewing duration, eating techniques, and the proper method of cutting foods. RESULTS: Changes in the masticatory, body composition, and biochemical indices were compared before and after the 6-month intervention. The values of body composition indices decreased significantly in both groups; however, the rate of change in body mass index significantly decreased in the MIG. In addition, the values of biochemical indices were significantly decreased in the MIG compared with that in the CTG, which is attributed to the addition of mastication instruction to female patients with obesity. CONCLUSION: Increasing the number of chews and duration of chewing times for carbohydrates, which are staple foods, possibly contributed to weight loss and improvement of glucose metabolism. TRIAL REGISTRATION: UMIN, UMIN000025875. Registered on 27 Jan 2017.

Serum Follistatin Levels are Independently Associated with Exercise Tolerance in Patients with Obesity.

OBJECTIVE: Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity. METHODS: In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m2) and severe obesity (BMI ≥35 kg/m2) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor. RESULTS: Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO2) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO2, MST, and irisin levels were independent predictors of FST levels. CONCLUSION: Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.

Personality traits and preoperative lifestyle improvement are predictors of early weight loss after sleeve gastrectomy.

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.

Validation of Earphone-Type Sensors for Non-Invasive and Objective Swallowing Function Assessment.

Standard methods for swallowing function evaluation are videofluoroscopy (VF) and videoendoscopy, which are invasive and have test limitations. We examined the use of an earphone-type sensor to noninvasively evaluate soft palate movement in comparison with VF. Six healthy adults wore earphone sensors and swallowed barium water while being filmed by VF. A light-emitting diode at the sensor tip irradiated infrared light into the ear canal, and a phototransistor received the reflected light to detect changes in ear canal movement, including that of the eardrum. Considering that the soft palate movement corresponded to the sensor waveform, a Bland-Altman analysis was performed on the difference in time recorded by each measurement method. The average difference between the time taken from the most downward retracted position before swallowing to the most upward position during swallowing of the soft palate in VF was -0.01 ± 0.14 s. The Bland-Altman analysis showed no fixed or proportional error. The minimal detectable change was 0.28 s. This is the first noninvasive swallowing function evaluation through the ear canal. The earphone-type sensor enabled us to measure the time from the most retracted to the most raised soft palate position during swallowing and validated this method for clinical application.

The relationship between changes in serum myostatin and adiponectin levels in patients with obesity undergoing a weight loss program.

BACKGROUND: An effective strategy for weight loss in patients who are overweight or obese is to reduce body fat mass while maintaining skeletal muscle mass. Adiponectin and myostatin are affected through changes in body composition due to weight loss, and examining their dynamics may contribute to strategies for maintaining skeletal muscle mass through weight loss. We aimed to examine the relationships among myostatin, adiponectin, and body composition, depending on the extent of weight loss, in patients with obesity undergoing a weight loss program. METHODS: We examined 66 patients with obesity (age: 46.8 ± 14.0 years, body mass index: 34.3 [31.0-38.4] kg/m2) attending a hospital weight loss program. We categorized the patients into two groups, namely an L group (those with a weight reduction of < 5% from baseline) and an M group (those with a weight reduction of > 5% from baseline). All patients underwent blood tests and were assessed for body composition, insulin resistance, adipocytokine and myokine levels, exercise tolerance, and muscle strength at baseline and post-intervention. RESULTS: Serum myostatin and adiponectin levels increased post-intervention in both groups. Body weight and %fat decreased, and the rate of lean body mass (%LBM) increased in both groups. Exercise capacity and muscle strength improved in the M group only. Change in (⊿) myostatin correlated with ⊿%fat, ⊿%LBM, and ⊿adiponectin. ⊿adiponectin (ß = - 0.262, p = 0.035) was an independent predictor of ⊿myostatin. CONCLUSIONS: Myostatin and adiponectin might cross-talk and regulate changes in skeletal muscle and fat mass with or without successful weight loss. These findings indicate that evaluating serum myostatin and adiponectin levels in clinical practice could be used to predict the effects of weight loss and help prevent skeletal muscle mass loss.

Improvements in exercise tolerance with an exercise intensity above the anaerobic threshold in patients with acute myocardial infarction.

Anaerobic threshold (AT) from cardiopulmonary exercise tests (CPX) is the standard for measuring exercise intensity among patients with cardiovascular disease in Japan. However, it remains controversial whether AT represents the safety limit for exercise intensity in patients with cardiovascular disease. The purpose of this study was to investigate cardiac rehabilitation (CR) efficacy and safety with exercise intensities above the AT and at a traditional AT in a randomized trial. The participants included 57 patients who were admitted to the outpatient CR unit with a diagnosis of acute myocardial infarction. The participants were randomly divided as follows: 25 patients in the AT group, who performed aerobic exercises with an intensity at the AT; and 32 patients in the "Over AT" group, who performed exercises at an intensity higher than the AT. The following components were measured: maximum oxygen uptake (peak VO2), oxygen uptake at the AT (AT VO2), increase in oxygen uptake during exercise (ΔVO2/ΔWR) during the CPX, vascular endothelial function test (%FMD: the percentage of flow-mediated dilation), and isometric knee extension strength. The measurements were obtained at the start of the exercise therapy and after 2, 3, and 4 months. They were compared within and between groups, and the correlation between the rates of improvement was investigated. Peak VO2, AT VO2, ΔVO2/ΔWR, and %FMD had significantly improved after 3 months in both groups. The isometric knee extension strength had improved in the "Over AT" group after 2 months. Interactions were observed with peak VO2, ΔVO2/ΔWR, and isometric knee extension strength. However, %FMD was not significantly different between the groups. In the "Over AT" group, the rate of improvement in peak VO2 was positively correlated with the improvement in the isometric knee extension strength (r = 0.61, p < 0.001), but not with %FMD. These data suggest that exercise at an intensity above the AT improved exercise tolerance faster than that at the AT, and this improvement rate was associated with changes in isometric knee extension strength.

Serum Angiopoietin-Like Protein 2 and NT-Pro BNP Levels and Their Associated Factors in Patients with Chronic Heart Failure Participating in a Phase III Cardiac Rehabilitation Program.

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Evaluation of oxygen uptake adjusted by skeletal muscle mass in cardiovascular disease patients with type 2 diabetes.

[Purpose] We aimed to evaluate oxygen uptake adjusted by total skeletal muscle mass in patients with cardiovascular disease with or without type 2 diabetes mellitus. [Participants and Methods] The participants included 54 males ≥50 years of age without heart failure who underwent cardiopulmonary exercise testing during cardiac rehabilitation. We divided the participants into two groups: patients with type 2 diabetes mellitus (DM group) and patients without type 2 diabetes mellitus (NDM group). [Results] We found no significant differences in age, weight, fat mass, or skeletal muscle mass between the groups. There were also no differences in cardiac function, body composition, and heart rate response. The DM group showed significantly lower peak oxygen uptake values adjusted by skeletal muscle mass, despite the absence of significant differences in skeletal muscle mass. A significant positive correlation was found between peak oxygen uptake and age, weight, and skeletal muscle mass. Stepwise regression analysis revealed that age, skeletal muscle mass, and medical history of diabetes were independent predictors of absolute peak oxygen uptake. [Conclusion] Peak oxygen uptake adjusted by skeletal muscle mass in patients with cardiovascular disease and type 2 diabetes mellitus is lower than that in those without type 2 diabetes mellitus.

Effect of exercise-based cardiac rehabilitation on non-culprit mild coronary plaques in the culprit coronary artery of patients with acute coronary syndrome.

Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P < 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P < 0.01). Peak VO2 in the CR group was significantly increased (P < 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS.

Effect of Mobility Restrictions During the Coronavirus Disease Epidemic on Body Composition and Exercise Tolerance in Patients With Obesity: Single Institutional Retrospective Cohort Study.

BACKGROUND: This study investigated the effects of mobility restrictions (MRs) during the COVID-19 epidemic on physical activity, body composition, and exercise tolerance in patients with obesity. METHODS: We analyzed data of obesity patients participating in a 6-month weight loss program in February 2020, and after, when the epidemic was considered to have had some effect on outdoor activity in Osaka, Japan (MR group). MR group patients were compared to patients with obesity attending the program in 2018 and 2019 (non-MR group) who had a similar number of months as MR group. Changes in physical activity, body composition, and exercise tolerance (O2 consumption; VO2) owing to the weight loss program were analyzed between both groups using analysis of covariance and logistic regression analysis. RESULTS: Decreases in body fat were significantly higher in MR group than in non-MR group. However, increases in physical activity, VO2 at anaerobic threshold, and peak VO2 were significantly lower in MR group; however, increases in peak VO2 owing to the weight loss program were less likely to be achieved in MR group (odds ratio, 0.21; 95% confidence interval, 0.06-0.81). CONCLUSION: MR during the COVID-19 epidemic may have affected the exercise tolerance of patients with obesity.

Masticatory Behaviors and Gender Differences in People with Obesity as Measured via an Earphone-Style Light-Sensor-Based Mastication Meter.

While people with obesity have been found to chew fewer times and for shorter durations, few studies have quantitatively evaluated mastication among this group. This study examined the relationship between the mastication characteristics of people with obesity and the factors correlated with obesity. To this end, 46 people with obesity and 41 healthy participants placed an earphone-style light sensor in the aperture of their outer ear. We also examined the partial correlation between this, their body composition, and various biochemical markers by gender. A two-way analysis of variance (ANOVA) regarding the masticatory index, gender, and the presence/absence of obesity for all three food items revealed the main effects in the gender difference and the presence/absence of obesity. Additionally, the number of times the salad was chewed showed an interaction between the gender and the presence/absence of obesity. In the BMI-corrected partial correlation analysis of the chewing index and the glucose/lipid metabolism index, the chewing time and the number of chews of all the food items negatively correlated with hemoglobin A1c(HbA1c), fasting plasma glucose (FPG), immunoreactive insulin (IRI), and homeostasis model assessment of insulin resistance (HOMA-R) in the female obese group. These findings might be used in weight-loss interventions for men with obesity and treatments that target the metabolic function among women with obesity.

Association of serum adiponectin and myostatin levels with skeletal muscle in patients with obesity: A cross-sectional study.

BACKGROUND: Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity. METHODS: Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples. RESULTS: The serum adiponectin level was 2.9 µg/mL (1.7-4.1 µg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1-2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001). CONCLUSION: The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.

Association of epigenetics of the PDK4 gene in skeletal muscle and peripheral blood with exercise therapy following artificial knee arthroplasty.

BACKGROUND: Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performing a tissue biopsy to investigate methylation of skeletal muscle fat metabolism genes is invasive, and less invasive and convenient alternatives such as blood testing are desired. However, the relationship between tissue and blood is still unclear. Here, we examined the relationship between DNA methylation of the PDK4 gene in skeletal muscle and peripheral blood. PATIENTS AND METHODS: Five patients who underwent artificial knee arthroplasty between April 2017 and June 2018 at Kansai Medical University Hospital were included (2 men and 3 women; average age, 75.2 years; body mass index, 26.1 kg/m2). We measured the body composition of the patients using dual-energy X-ray absorptiometry. Peripheral blood was collected at the time of hospitalization and 5 months after surgery; skeletal muscles were collected at the time of surgery and 5 months after surgery. Rehabilitation was performed according to the clinical procedure for 3 months after surgery. Patients performed resistance training and aerobic exercise using an ergometer for 20 min twice a week. Biopsy samples were treated with bisulfite after DNA extraction, and the methylation rate was calculated at different CpG islands downstream from the transcription initiation codon of the PDK4 gene. RESULTS: No significant change in body composition was observed before and after postoperative exercise therapy, and no significant change was noted in the methylation at each position in the promoter region of PDK4 in the skeletal muscle and peripheral blood. However, changes in the methylation rate at CpG1 in peripheral blood significantly correlated with those in skeletal muscle (P = 0.037). Furthermore, the amount of change in the methylation rate of CpG1 in the skeletal muscle was significantly correlated (P = 0.037) with the average methylation rate at the promoter region in peripheral blood. CONCLUSIONS: Methylation rates at CpG1 in the skeletal muscle and peripheral blood were significantly correlated, suggesting that skeletal muscle methylation could be analyzed via peripheral blood rather than skeletal muscle biopsy.

Prevalence and risk factors of sarcopenia in community-dwelling older adults visiting regional medical institutions from the Kadoma Sarcopenia Study.

This study aimed to investigate risk factors for sarcopenia in community-dwelling older adults visiting regional medical institutions. We retrospectively analyzed medical records of 552 participants (mean age: 74.6 ± 6.7 years, males 31.3%) who underwent body composition evaluation between March 2017 and December 2018 at one of 24 medical institutions belonging to the Kadoma City Medical Association in Japan. We collected the participant's characteristics and laboratory data. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019. Sarcopenia, including severe sarcopenia, was detected in 22.3% of all participants, 17.3% of men, and 24.5% of women; rates increased with age. Multivariate logistic regression analysis revealed age (odds ratio [OR]: 2.12; 95% confidence interval [CI] 1.20-3.75), obesity (OR: 0.15; 95% CI 0.07-0.32), hypertension (OR: 0.44; 95% CI 0.25-0.76), certification of long term care (OR: 3.32; 95% CI 1.41-7.81), number of daily conversations (OR: 0.44; 95% CI 0.25-0.77), and malnutrition (OR: 2.42; 95% CI 1.04-5.60) as independent predictors of sarcopenia. Receiver operating characteristic curve analysis demonstrated that the cut-off for daily conversations defining sarcopenia was 4.8 persons. The prevalence of sarcopenia in this study was 22.3%. Besides traditional risk factors for sarcopenia, the number of daily conversations was an independent factor.

Changes in Body Composition and FTO Whole Blood DNA Methylation Among Japanese Women: A Randomized Clinical Trial of Weight-Loss Program.

OBJECTIVE: DNA methylation is an epigenetic mechanism that regulates gene expression. The obesity-related (FTO) gene is the first gene found to be associated with fat mass and obesity. However, no studies have examined the relationship between weight-loss intervention effect and FTO methylation in obese individuals with whole blood DNA. The purpose of this study was to quantify FTO whole blood DNA methylation and investigate the relationship between body composition, exercise capacity, and blood parameters with a 6-month weight-loss program intervention. PARTICIPANTS AND METHODS: Eighteen female participants (mean age, 50.6 ±12.1 years, body mass index (BMI), 33.5 ± 6.2 kg/m2) who completed a 6-month weight-loss program at the obesity outpatient department at the Health Science Center of Kansai Medical University Hospital from March 2017 to October 2018 were included in the analysis. Participants were randomized into a normal treatment group (NTG) and a group with additional resistance training (RTG). Body composition, exercise tolerance and metabolic index were measured in each participant. DNA methylation status in whole blood samples was determined using pyrosequencing. All measurements were taken during the first visit and at the 6-month post-intervention visit. RESULTS: The methylation rate was significantly decreased in the NTG in CpG1 (p=0.011) and total value of CpG (p=0.011), whereas in the treatment group containing resistance training (RTG), CpG3 (p=0.038) was increased significantly. Furthermore, the independent factors that determine %CpG3 of RTG were visceral fat area change rate (%VFA) (ß = -0.568, P = 0.007, R2 = 0.527) and resistance training (ß = 0.517, P = 0.012, R2 = 0.527), which have been extracted. CONCLUSION: A 6-month weight-loss program, including resistance training, may be associated with decreased visceral fat area changes and increased RTG CpG3 methylation changes. However, further replication studies with larger sample sizes are warranted to verify the findings of this study.

Epigenetic mechanism controls PDK4 gene activation before and after exercise therapy following artificial knee arthroplasty.

PURPOSE: DNA methylation is thought to play a role in exercise-induced gene expression. We aimed to examine changes in muscular strength and body composition in elderly patients with end-stage knee osteoarthritis before and after artificial knee arthroplasty and exercise therapy. We aimed to confirm the relationship between DNA methylation and body composition, using the methylation rate of the pyruvate dehydrogenase kinase 4 (PDK4) gene that regulates skeletal muscle and fat metabolism. PATIENTS AND METHODS: Patients underwent artificial knee arthroplasty between April 2017 and June 2017 at Kansai Medical University Hospital. Six patients (seven knees) were included in the analysis (four males/two females; average age, 75.7 years; body mass index, 25.1 kg/m2). Body composition and knee extension muscle strength were measured before surgery and 5 months after surgery. Rehabilitation was performed for 3 months after surgery. In the remaining 2 months, patients performed resistance training and aerobic exercise using an ergometer for 20 mins, twice a week. A biopsy of the vastus medialis was taken during surgery and 5 months post-surgery. Biopsy samples were treated with bisulfite after DNA extraction, and DNA methylation rate was calculated. RESULTS: Body weight (P=0.046), total weight (P=0.027), and total fat mass (P=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the PDK4 gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, P=0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, P=0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, P=0.05). CONCLUSION: Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the PDK4 gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.

The effects of toe grip training on physical performance and cognitive function of nursing home residents.

BACKGROUND: Toe grip-related training requires individuals to actively exercise muscles that are not frequently used; therefore, it may improve not only toe grip strength but also cognitive function. The purpose of this study was to examine the effects of toe grip-related training on predictors of physical performance and cognitive function in nursing home residents. METHODS: A total of 35 nursing home residents (35 left and 35 right feet; mean age, 82.1 ± 7.9 years) were included in this study. The participants were divided into two groups: a training group and a control group. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of the participants, and the Fall Risk Index (FRI) was used to evaluate the risk of falls. Toe grip-related physical function was also assessed. Baseline endpoints were evaluated and the effects of toe grip-related training were examined following a 12-week training intervention. RESULTS: The training group showed significant improvements in MMSE score, FRI score, toe grip strength, and the toe skill (TS) test; however, the control group did not show these changes. The training group showed significant increases in Δ MMSE, Δ toe grip strength, and Δ TS (right foot) than the control group. Stepwise regression analysis revealed that Δ toe grip strength is an independent factor of Δ MMSE. CONCLUSIONS: Toe grip training improves not only toe grip strength itself, but also cognitive function. Furthermore, change in toe grip strength was an independent factor of change in MMSE in those populations. TRIAL REGISTRATION: UMIN, UMIN000027437 . Registered on 26 May 2017.

Association of locomotive activity with sleep latency and cognitive function of elderly patients with cardiovascular disease in the maintenance phase of cardiac rehabilitation.

BACKGROUND: Because of the advanced age of patients with cardiovascular disease (CVD), prevention of sleep disorder and dementia is a priority for cardiac rehabilitation (CR) during their long-term care. This study aimed to investigate the association of physical activity with sleep quality and cognitive function in elderly patients with CVD in the CR maintenance phase. METHODS: We conducted a multicenter study through the Clinical Exercise Physiology Association Japan network, which included 102 elderly patients (mean age, 74±7.4 years) with CVD undergoing phase III CR at 6 institutions. Physical activity was assessed using a triaxial accelerometer for 7 consecutive days and was classified as locomotive and household activities. Physical fitness was assessed via 6-min walking distance (6MD), hand grip power, 10-m walking speed, one leg standing time with eyes open, and 10 times sit-to-stand tests. Sleep quality and cognitive function were evaluated using the Pittsburgh sleep quality index (PSQI) and mini-mental state examination (MMSE) scores, respectively. RESULTS: The patients performed 5506.8±3743.6 steps/day and scored 5.8±3.5 points in the PSQI and 28.4±1.7 points in the MMSE. Sleep latency and MMSE scores correlated with locomotive activity, but not with household activity. Locomotive activity and 6MD were independent predictors of sleep latency and MMSE score, respectively. When patients with heart failure were excluded, the relationship between sleep latency and locomotive activity was preserved, but the relationship between exercise tolerance and cognitive function disappeared. CONCLUSION: Locomotive activity and exercise tolerance are associated with sleep latency and cognitive function in elderly patients with CVD continuing phase III CR. However, in this study, the relationship between exercise tolerance and cognitive function was offset by the presence of heart failure.

Relationship between Homocysteine, Folate, Vitamin B12 and Physical Performance in the Institutionalized Elderly.

Hyperhomocysteinemia causes various diseases including cardiovascular disease, osteoporotic fracture and dementia. Although there have been reports that hyperhomocysteinemia decreases physical performance, findings are inconsistent on the association of homocysteine, folate, vitamin B12 and physical performance. Considering that lower physical performance increases the risk of fall and fracture in the elderly, the effect of nutritional status on physical function must be clarified. This is a cross-sectional study conducted from April 2015 to November 2016. Eighty-six residents and users in five care facilities were evaluated for their blood homocysteine, folate and vitamin B12 concentrations and indices for physical performance; lower limb muscle strength, handgrip strength and gait speed. Analyses of physical performance were done in women only, considering the high proportion of women in the study population and the muscular gender difference. In the third tertile of plasma homocysteine concentration, handgrip strength was significantly lower than in the first tertile (p=0.027). In the first tertile of serum folate concentration, handgrip strength was significantly lower than in the third tertile (p=0.002). Although not statistically significant, lower limb muscle strength in the third tertile of folate was higher than in the first (p=0.061) and second (p=0.057) tertile. In the multiple regression analysis, however, only serum folate concentration was a significant contributor except for age. In subjects with their serum folate and vitamin B12 concentrations both exceeding the median, lower limb muscle strength was higher. Low serum folate concentration is a risk factor for lower physical performance independent of homocysteine in elderly women.