Yoshio Nakata

Variations in the FTO gene are associated with severe obesity in the Japanese

AbstractVariations in the fat-mass and obesity-associated gene (FTO) are associated with the obesity phenotype in many Caucasian populations. This association with the obesity phenotype is not clear in the Japanese. To investigate the relationship between the FTO gene and obesity in the Japanese, we genotyped single nucleotide polymorphisms (SNPs) in the FTO genes from severely obese subjects [n = 927, body mass index (BMI) ≥ 30 kg/m2] and normal-weight control subjects (n = 1,527, BMI < 25 kg/m2). A case-control association analysis revealed that 15 SNPs, including rs9939609 and rs1121980, in a linkage disequilibrium (LD) block of approximately 50 kb demonstrated significant associations with obesity; rs1558902 was most significantly associated with obesity. P value in additive mode was 0.0000041, and odds ratio (OR) adjusted for age and gender was 1.41 [95% confidential interval (CI) = 1.22–1.62]. Obesity-associated phenotypes, which include the level of plasma glucose, hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and blood pressure were not associated with the rs1558902 genotype. Thus, the SNPs in the FTO gene were found to be associated with obesity, i.e., severe obesity, in the Japanese.

Regional Body Composition Changes Exhibit Opposing Effects on Coronary Heart Disease Risk Factors

Objective—We investigated how regional body composition measured by dual-energy X-ray absorptiometry (DXA) is associated with risk factors for coronary heart disease (CHD) during weight reduction in obese women. Methods and Results—Data were gathered from 128 overweight and obese women, aged 34 to 66 years, during a 14-week intervention study with diet and exercise. Regional (arms, legs, and trunk) fat tissue (FT) and lean soft tissue (LST) were measured by DXA. The FT change in legs correlated negatively with changes in diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and the number of CHD risk factors per subject (r =−0.17, P< 0.05 to −0.26, P< 0.01) in response to weight reduction, whereas truncal FT change had positive correlations with changes in triglycerides, LDL-C, FPG, and the number of CHD risk factors per subject (r= 0.17, P< 0.05 to 0.25, P< 0.01). LST change in legs correlated negatively with changes in systolic blood pressure, FPG, and the number of risk factors (r=− 0.20 to −0.21, P <0.05). Conclusions—Regional body composition information is important for evaluating improvement of CHD risk factors during weight-reduction treatment for obesity; differential FTs had opposing effects on CHD risk factors during weight reduction in obese women.

Prevention of atrial fibrillation recurrence with corticosteroids after radiofrequency catheter ablation: a randomized controlled trial.

OBJECTIVES We sought to clarify the efficacy of corticosteroid therapy for preventing atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). BACKGROUND The inflammatory process may cause acute AF recurrence after PVI. However, no studies have examined the relationship between corticosteroid administration and AF recurrence after PVI. METHODS A total of 125 patients with paroxysmal AF were randomized to receive either corticosteroids (corticosteroid group) or a placebo (placebo group). In the corticosteroid group, intravenous hydrocortisone (2 mg/kg) was given the day of the procedure, and oral prednisolone (0.5 mg/kg/day) was administered for 3 days after the PVI. The body temperature and high-sensitivity C-reactive protein level were measured before and on each of the first 3 days after ablation. RESULTS The prevalence of immediate AF recurrence (≤3 days after the PVI) was significantly lower in the corticosteroid group (7%) than in the placebo group (31%). The maximum body temperature and C-reactive protein during the initial 3 days after ablation and the increase in the body temperature and C-reactive protein level from baseline were significantly lower in the corticosteroid group than in the placebo group. Corticosteroid treatment did not decrease AF recurrences between 4 and 30 days after ablation. The AF-free rate at 14 months post-ablation was greater in the corticosteroid group (85%) than in the placebo group (71%, p=0.032 by the log-rank test). CONCLUSIONS Transient use of small amounts of corticosteroids shortly after AF ablation may be effective and safe for preventing not only immediate AF recurrences but also AF recurrences during the mid-term follow-up period after PVI.

Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population

There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) ⩾30 kg m−2) and normal-weight control subjects (n=1736, BMI <25 kg m−2). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.

Feasibility of rehabilitation training with a newly developed wearable robot for patients with limited mobility

OBJECTIVE To investigate the feasibility of rehabilitation training with a new wearable robot. DESIGN Before-after clinical intervention. SETTING University hospital and private rehabilitation facilities. PARTICIPANTS A convenience sample of patients (N=38) with limited mobility. The underlying diseases were stroke (n=12), spinal cord injuries (n=8), musculoskeletal diseases (n=4), and other diseases (n=14). INTERVENTIONS The patients received 90-minute training with a wearable robot twice per week for 8 weeks (16 sessions). MAIN OUTCOME MEASURES Functional ambulation was assessed with the 10-m walk test (10MWT) and the Timed Up & Go (TUG) test, and balance ability was assessed with the Berg Balance Scale (BBS). Both assessments were performed at baseline and after rehabilitation. RESULTS Thirty-two patients completed 16 sessions of training with the wearable robot. The results of the 10MWT included significant improvements in gait speed, number of steps, and cadence. Although improvements were observed, as measured with the TUG test and BBS, the results were not statistically significant. No serious adverse events were observed during the training. CONCLUSIONS Eight weeks of rehabilitative training with the wearable robot (16 sessions of 90min) could be performed safely and effectively, even many years after the subjects received their diagnosis.

Effect of weight reduction with dietary intervention on arterial distensibility and endothelial function in obese men

Obesity and reduction in central arterial distensibility, respectively, have been identified as powerful and independent risk factors for cardiovascular disease. However, the effect of weight reduction on central arterial function in obese subjects has not yet been clarified. We investigated whether low-calorie diet-induced weight reduction affects central arterial distensibility and endothelial function in middle-aged obese men. Twelve obese men (age: 45+2 yrs, BMI: 30+1 kg/m 2) completed a 12-week dietary intervention. Caloric restriction induced significantly weight loss and decrease in BMI. After the program, carotid arterial compliance significantly increased and b-stiffness index and aortic pulse-wave velocity remarkably decreased. Concentrations of plasma endothelin-1 (ET-1) significantly decreased and plasma nitric oxide (NO) markedly increased after the program. Weight reduction by low-calorie diet in obese men increases central arterial distensibility, which may contribute to the improvement in endothelial function, as noted by a decrease in ET-1 and an increase in NO.

Effects of Aerobic Exercise on Metabolic Syndrome Improvement in Response to Weight Reduction

Objective: The objective was to test effects of aerobic exercise training on metabolic syndrome (MetSyn) improvement in response to weight reduction.

Association of variations in the FTO , SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population

Metabolic syndrome is defined as a cluster of multiple risk factors, including central obesity, dyslipidemia, hypertension and impaired glucose tolerance, that increase cardiovascular disease morbidity and mortality. Genetic factors are important in the development of metabolic syndrome, as are environmental factors. However, the genetic background of metabolic syndrome is not yet fully clarified. There is evidence that obesity and obesity-related phenotypes are associated with variations in several genes, including NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, SH2B1, FTO, MAF, MC4R, KCTD15, SCG3, MTMR9, TFAP2B, MSRA, LYPLAL1, GCKR and FADS1. To investigate the relationship between metabolic syndrome and variations in these genes in the Japanese population, we genotyped 33 single-nucleotide polymorphisms (SNPs) in 19 genes from 1096 patients with metabolic syndrome and 581 control individuals who had no risk factors for metabolic syndrome. Four SNPs in the FTO gene were significantly related to metabolic syndrome: rs9939609 (P=0.00013), rs8050136 (P=0.00011), rs1558902 (P=6.6 × 10−5) and rs1421085 (P=7.4 × 10−5). rs3764220 in the SCG3 gene (P=0.0010) and rs2293855 in the MTMR9 gene (P=0.0015) were also significantly associated with metabolic syndrome. SNPs in the FTO, SCG3 and MTMR9 genes had no SNP × SNP epistatic effects on metabolic syndrome. Our data suggest that genetic variations in the FTO, SCG3 and MTMR9 genes independently influence the risk of metabolic syndrome.

Effects of aerobic exercise and obesity phenotype on abdominal fat reduction in response to weight loss

OBJECTIVE:To test the effects on abdominal fat reduction of adding aerobic exercise training to a diet program and obesity phenotype in response to weight loss.DESIGN:A prospective clinical trial with a 14-week weight-loss intervention design.SETTING AND PARTICIPANTS:In total, 209 overweight and obese women were assigned to four subgroups depending on type of treatment and the subjects obesity phenotype: diet alone (DA) with intra-abdominal fat (IF) obesity (≥mean IF area), diet plus exercise (DE) with IF obesity, DA with abdominal subcutaneous fat (ASF) obesity (<mean IF area) and DE with ASF obesity. Abdominal fat areas were evaluated by CT scans, with values adjusted for selected variables.RESULTS:Values were adjusted for age, menopausal status and change in body weight and total fat mass. The IF reductions were significantly (P<0.0001) greater in subjects with IF obesity phenotype (−45.1 cm2) compared to the ASF obesity phenotype (−22.2 cm2). The ASF reductions were significantly (P<0.001) greater for subjects with ASF obesity (−74.5 cm2) compared to IF obesity (−55.5 cm2). For IF obesity, the IF reduction was significantly (P<0.01) greater in the DE group (−49.3 cm2) than in the DA group (−37.8 cm2).CONCLUSION:These results suggest that for individuals with IF obesity, the efficacy on reducing IF of adding aerobic exercise training to a diet-alone weight-reduction program is more prominent (−49.3 cm2/−37.8 cm2=1.3 times) compared with DA. Moreover, abdominal fat reduction was found to be modified by obesity phenotype in response to weight loss.

Effect of Habitual Aerobic Exercise on Body Weight and Arterial Function in Overweight and Obese Men

The effect of habitual exercise on vascular function, including central arterial distensibility and endothelial function, in obese subjects has not yet been clarified. We investigated whether aerobic exercise training affects central arterial distensibility and endothelial function in middle-age overweight and obese men. A total of 21 overweight and obese men (age 50 +/- 2 years, body mass index 30 +/- 1 kg/m(2)) completed a 12-week aerobic exercise intervention. Aerobic exercise training significantly reduced their body weight and resulted in a significant decrease in body mass index. After the weight-reduction exercise program, carotid arterial compliance (determined by simultaneous B-mode ultrasonography and arterial applanation tonometry on the common carotid artery) significantly increased; and the beta-stiffness index, an index of arterial compliance adjusted for distending pressure, significantly decreased. The concentrations of plasma endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, significantly decreased and plasma nitric oxide (measured as the stable end product [nitrite/nitrate]), a potent vasodilator produced by vascular endothelial cells, significantly increased after the weight-reduction exercise program. In conclusion, weight reduction by aerobic exercise training in overweight and obese men increased the central arterial distensibility. This increase might contribute to the improvement in endothelial function, as assessed by a decrease in endothelin-1 and an increase in nitric oxide, after exercise training-induced weight loss.