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Haruhiko Nishida,1 Katsuko Onishi,1 Satoshi Kurose,1 Hiromi Tsutsumi,1 Takumi Miyauchi,2 Nana Takao,2 Sawako Yoshiuchi,2 Aya Fujii,2 Yutaka Kimura1,2 1Department of Health Science, Kansai Medical University, Osaka, Japan; 2Health Science Center, Kansai Medical University, Osaka, JapanCorrespondence: Haruhiko NishidaDepartment of Health Science, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, JapanTel +81 72 804 2334Fax +81 72 804 2548Email nishidah@hirakata.kmu.ac.jpObjective: 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) (β = − 0.568, P = 0.007, R2 = 0.527) and resistance training (β = 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.Keywords: epigenetics, obesity, body composition, resistance training

Background: A comprehensive cardiac rehabilitation (CR) program is recommended for coronary artery disease (CAD). However, many facilities do not have established programs for dietary guidance and patient education, resulting in an exercise-based CR program and limited efficacy for secondary prevention., Methods and Results: A pilot study will be conducted to develop an online Japanese-style intensive cardiac rehabilitation (J-ICR) program for Japanese patients with CAD and will examine adherence, safety, and efficacy. Twenty-four patients diagnosed with stable CAD will be randomly assigned in a 1 : 1 ratio to either an early or late-phase group. The program will comprise the following four parts: exercise sessions; dietary education centered on "the Japan diet"; mindfulness; and group support, with a frequency of 3 h per session, once a week for 12 weeks (a total of 36 h). The primary endpoint will be program feasibility, determined by examining its adherence. Physical examination and function, stress-coping skills, risk of classic CAD (e.g., lipid profile, glucose tolerance, and blood pressure), and dietary changes will be assessed as secondary endpoints., Conclusions: The online J-ICR program is designed as a comprehensive CR program for Japanese patients with CAD. If this program shows high adherence and an improvement in CAD risk factors, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers., Competing Interests: K.O. is a member of Circulation Reports’ Editorial Team. The authors declare that there are no conflicts of interest. Conflicts of interest were reviewed by the Kyoto University Clinical Research Conflict of Interest Review Committee in accordance with the Kyoto University Conflict of Interest Policy and Kyoto University Conflict of Interest Management Regulations., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

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., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

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., (© 2023. The Author(s).)

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.

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.

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/m 2 ) 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 (β = - 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.

Introduction: The increased visceral fat in patients with obesity can increase the technical difficulty of surgery. This study was performed to evaluate a preoperative 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer., Methods: This prospective single-center study involved patients with obesity who were planning to undergo laparoscopic gastrectomy for gastric cancer. Obesity was defined according to the Japanese criteria: BMI ≥25 kg/m 2 or waist circumference ≥85 cm in men and ≥90 cm in women. The patients underwent a preoperative 20-day very low-calorie diet and received nutritional counseling. Weight loss, body composition, visceral fat mass, and operative outcomes were evaluated., Results: Thirty-three patients were enrolled from September 2013 to August 2015. Their median age was 71 years, and 78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8-82.5 kg) and 26.0 kg/m 2 (range, 23.5-31.0 kg/m 2 ), respectively. The patients achieved a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8-5.1), corresponding to 3.2 kg (95%CI: 2.7-3.7 kg). Body fat mass was significantly decreased by a mean of 2.5 kg (95%CI: 1.9-3.1), whereas skeletal muscle mass was unaffected (mean: -0.20 kg [95%CI: -0.55-0.15]). The visceral fat mass reduction rate was high as 16.8% (range, 11.6%-22.0%). All patients underwent laparoscopic gastrectomy as planned. Severe postoperative morbidity (Clavien-Dindo grade ≥III) was seen in only one patient (3.0%)., Conclusion: The preoperative 20-day very low-calorie diet weight loss program is promising for the treatment of obesity before laparoscopic gastrectomy for gastric cancer., (© 2018 The Authors. Asian Journal of Endoscopic Surgery published by John Wiley & Sons Ltd on behalf of Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force.)

The epidemic of obesity is now a major public health concern in many parts of the world. Face-to-face tailored lifestyle modification therapy is one of the major approaches used for weight loss. However, the lack of time for multiple visits and the lack of resources for administering therapy hinder its implementation. We administered a web-based weight loss program for obese patients from July 2010 to January 2012 that required only 2 personal interviews over 6 months. The program used a system of auto-extraction of behavioural objectives and auto recording of daily weight and number of steps taken. The subjects included 3 obese men (mean age, 35.7 ± 2.3 years; mean body mass index (BMI), 30.4 ± 0.8 kg/m²) and 17 obese women (mean age, 39.3 ± 9.5 years; mean BMI, 28.1 ± 1.8 kg/m2) who volunteered to participate in this weight loss program. Weight loss achieved through this program was significant (mean, 2.7%, p=0.047). Abdominal visceral fat area (VFA) decreased significantly (mean, 12.6%, p=0.017), and the serum cholinesterase and alanine aminotransferase levels improved (mean, 33 U/L, p=0.003; mean, 7 IU/L, p=0.033 respectively). Metabolic syndrome criteria number had a tendency to decrease. Dietary and nutrient intake levels on the food frequency questionnaire improved. Weight loss ratio after 6 months and initial weight loss ratio were strongly significantly correlated. A web-based weight loss program with auto-extraction of behavioural objectives and recording of daily weight and steps can achieve weight loss, as determined by VFA reduction, on low manpower.

Background: The aim of this study was to examine the outcomes of exercise therapy in patients with hepatocellular carcinoma who underwent hepatectomy., Methods: Fifty-one patients with hepatocellular carcinoma were randomized to diet therapy alone (n = 25) or to exercise in addition to diet therapy (n = 26). Exercise at the anaerobic threshold of each patient was started 1 month preoperatively, resumed from 1 week postoperatively, and continued for 6 months., Results: Whole body mass and fat mass in the exercise group compared with the diet group were significantly decreased at 6 months postoperatively. Fasting serum insulin and the homeostasis model assessment score were also significantly decreased. At 6 months, anaerobic threshold and peak oxygen consumption were significantly increased, while serum insulin and insulin resistance were significantly improved in a high-frequency exercise subgroup compared with a low-frequency group., Conclusions: Perioperative exercise therapy for patients with hepatocellular carcinoma with liver dysfunction may improve insulin resistance associated with hepatic impairment and suggests a benefit to the early resumption of daily exercise after hepatectomy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy., Methods: Sixty-one HCC patients underwent preoperative cardiopulmonary exercise testing to determine their anaerobic threshold (AT). The AT was defined as the break point between carbon dioxide production and oxygen consumption per unit of time (VO₂). Postoperative events including recurrence of HCC, death, liver failure, and complications of cirrhosis were recorded. Univariate and multivariate analyses were performed to evaluate associations between 35 clinical factors and outcomes, and identify independent prognostic indicators of event-free survival and maintenance of Child-Pugh class., Results: Multivariate analyses identified preoperative branched-chain amino acid/tyrosine ratio (BTR) <5, alanine aminotransferase level ≥42 IU/l, and AT VO₂ <11.5 ml/min/kg as independent prognostic indicators of event-free survival. AT VO2 <11.5 ml/min/kg and BTR <5 were identified as independent prognostic indicators of maintenance of Child-Pugh class., Conclusions: This study identified preoperative exercise capacity as an independent prognostic indicator of event-free survival and maintenance of Child-Pugh class in HCC patients with chronic liver injury undergoing hepatectomy.

A formin Bni1p nucleates actin to assemble actin cables, which guide the polarized transport of secretory vesicles in budding yeast. We identified mutations that suppressed both the lethality and the excessive actin cable formation caused by overexpression of a truncated Bni1p (BNI1DeltaN). Two recessive mutations, act1-301 in the actin gene and sla2-82 in a gene involved in cortical actin patch assembly, were identified. The isolation of sla2-82 was unexpected, because cortical actin patches are required for the internalization step of endocytosis. Both act1-301 and sla2-82 exhibited synthetic growth defects with bni1Delta. act1-301, which resulted in an E117K substitution, interacted genetically with mutations in profilin (PFY1) and BUD6, suggesting that Act1-301p was not fully functional in formin-mediated polymerization. sla2-82 also interacted genetically with genes involved in actin cable assembly. Some experiments, however, suggested that the effects of sla2-82 were caused by depletion of actin monomers, because the temperature-sensitive growth phenotype of the bni1Delta sla2-82 mutant was suppressed by increased expression of ACT1. The isolation of suppressors of the BNI1DeltaN phenotype may provide a useful system for identification of actin amino-acid residues that are important for formin-mediated actin polymerization and mutations that affect the availability of actin monomers.

Septins are filament-forming proteins that function in cytokinesis in a wide variety of organisms. In budding yeast, the small GTPase Cdc42p triggers the recruitment of septins to the incipient budding site and the assembly of septins into a ring. We herein report that Bni1p and Cla4p, effectors of Cdc42p, are required for the assembly of the septin ring during the initiation of budding but not for its maintenance after the ring converts to a septin collar. In bni1Delta cla4-75-td mutant, septins were recruited to the incipient budding site. However, the septin ring was not assembled, and septins remained at the polarized growing sites. Bni1p, a formin family protein, is a member of the polarisome complex with Spa2p, Bud6p, and Pea2p. All spa2Delta cla4-75-td, bud6Delta cla4-75-td, and pea2Delta cla4-75-td mutants showed defects in septin ring assembly. Bni1p stimulates actin polymerization for the formation of actin cables. Point mutants of BNI1 that are specifically defective in actin cable formation also exhibited septin ring assembly defects in the absence of Cla4p. Consistently, treatment of cla4Delta mutant with the actin inhibitor latrunculin A inhibited septin ring assembly. Our results suggest that polarisome components and Cla4p are required for the initial assembly of the septin ring and that the actin cytoskeleton is involved in this process.