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The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference, waist-hip ratio measurements and visceral fat area (VFA); the latter can be accurately measured by performing computed tomography (CT). In addition to environmental factors, genetic factors play an important role in obesity and fat distribution. New genetic loci associated with body mass index (BMI) and adiposity have been identified by genome-wide association studies (GWASs). This study utilized CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to higher BMI are associated with VFA, subcutaneous fat area (SFA), and the ratio of VFA to SFA (V/S ratio). We measured the VFA and SFA of 1424 obese Japanese subjects (BMI ≥ 25 kg/m(2), 635 men and 789 women) who were genotyped for 13 single nucleotide polymorphisms (SNPs) reported by recent GWASs, namely, TNNI3K rs1514175, PTBP2 rs1555543, ADCY3 rs713586, IRS1 rs2943650, POC5 rs2112347, NUDT3 rs206936, LINGO2 rs10968576, STK33 rs4929949, MTIF3 rs4771122, SPRY2 rs534870, MAP2K5 rs2241423, QPCTL rs2287019, and ZC3H4 rs3810291. The G-allele of NUDT3 rs206936 was significantly associated with increased BMI (P = 5.3 × 10(-5)) and SFA (P = 0.00039) in the obese Japanese women. After adjustment with BMI, the association between rs206936 and SFA was not observed. This significant association was not observed in the men. The other SNPs analyzed were not significantly associated with BMI, VFA, SFA, or V/S ratio. Our results suggest that NUDT3 rs206936 is associated with BMI in Japanese women.

Visceral fat accumulation has an important role in increasing morbidity and mortality rate by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of obesity have been identified by genome-wide association studies in Caucasian populations. We genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography (CT) for measuring visceral fat area (VFA) and subcutaneous fat area (SFA), for the following single-nucleotide polymorphisms (SNPs): NEGR1 rs2815752, SEC16B rs10913469, TMEM18 rs6548238, ETV5 rs7647305, GNPDA2 rs10938397, BDNF rs6265 and rs925946, MTCH2 rs10838738, SH2B1 rs7498665, MAF rs1424233, and KCTD15 rs29941 and rs11084753. In the additive model, none of the SNPs were significantly associated with body mass index (BMI). The SH2B1 rs7498665 risk allele was found to be significantly associated with VFA (P=0.00047) but not with BMI or SFA. When the analysis was performed in men and women separately, no significant associations with VFA were observed (P=0.0099 in men and P=0.022 in women). None of the other SNPs were significantly associated with SFA. Our results suggest that there is a VFA-specific genetic factor and that a polymorphism in the SH2B1 gene influences the risk of visceral fat accumulation.

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) > or =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.

Objective: The link between uric acid levels and metabolic syndrome was investigated., Methods: We used data for 997 men and 1290 women. Metabolic syndrome was defined by a new criterion in Japan and uric acid was measured., Results: Subjects who did not drink alcohol were evaluated. Uric acid was significantly higher in subjects with metabolic syndrome compared with subjects without the syndrome in both sexes. The presence of abdominal obesity and dyslipidemia in men and abdominal obesity in women revealed positive impacts on uric acid levels., Conclusion: High serum uric acid may be often associated with metabolic syndrome in Japanese people, which accelerates the development of cardiovascular disease from metabolic syndrome.

Objective: We investigated the link between a reduction in waist circumference and metabolic syndrome., Methods: 105 obese Japanese men were enrolled in this study with a 1-year follow-up. Anthropometric and body composition parameters, i.e. height, body weight, body fat percentage, waist circumference and hip circumference, blood pressure, triglyceride, HDL cholesterol and blood sugar, were evaluated. Metabolic syndrome was diagnosed using criteria developed in Japan., Results: After a 1-year follow-up, the parameters of metabolic syndrome were significantly improved. The prevalence of metabolic syndrome was significantly reduced in subjects with at least 3 cm of waist circumference reduction (Group R). However, in subjects without such reduction (Group C), the prevalence of metabolic syndrome was similar to baseline levels. The prevalence of abdominal obesity, hypertension and dyslipidemia was also significantly reduced in Group R. In addition, there were remarkable differences of delta triglyceride (delta represents positive changes in parameters) and delta HDL cholesterol between Group R and Group C., Conclusion: At least 3 cm of waist circumference reduction may be beneficial for improving metabolic syndrome in obese Japanese men.

Objective: Chronic inflammation observed in obesity has been reported to be implicated in the development of atherosclerosis. We screened candidate chemokines that link chronic inflammation and obesity., Research Methods and Procedures: Japanese overweight (n = 39, BMI 28.7 +/- 0.65 kg/m(2)) and normal-weight (n = 24, BMI 22.3 +/- 0.45 kg/m(2)) subjects were enrolled. Using antibody-based protein microarray, spot intensities of monocyte chemoattractant protein (MCP)-4, eotaxin, and eotaxin-2 correlated with anthropometric parameters. We further measured serum concentration of these chemokines and mRNA levels in adipose tissues obtained from volunteers., Results: Serum MCP-4 levels showed positive correlation with BMI (r = 0.318, p = 0.014), waist (r = 0.316, p = 0.018), and waist-to-hip ratio (WHR) (r = 0.264, p = 0.049). Furthermore, MCP-4 correlated with homeostasis model assessment of insulin resistance (r = 0.392, p = 0.002), high-sensitivity C-reactive protein (hsCRP) (r = 0.350, p = 0.006). In step-wise multiple regression analyses, hsCRP independently correlated with MCP-4 levels. The expression of MCP-4 mRNA in visceral adipose tissue positively correlates with BMI. Serum eotaxin levels correlate with BMI (r = 0.262, p = 0.045) and WHR (r = 0.383, p = 0.003). Serum eotaxin-2 levels correlated with BMI (r = 0.464, p < 0.001), waist (r = 0.333, p = 0.017), and WHR (r = 0.278, p = 0.048). However, eotaxin and eotaxin-2 levels did not show significant correlation with hsCRP., Discussion: Serum levels of MCP-4, eotaxin, and eotaxin-2, which belong to CC chemokine family and share CC chemokine receptor 3, correlated with BMI. These chemokines, especially MCP-4, may be critical molecules that link obesity and chronic inflammation.

Objective: To investigate the difference between air displacement plethysmograph (ADP) and bioelectrical impedance (BI) for assessing body composition changes during weight loss in Japanese women., Design: Cross-sectional and longitudinal investigation study., Subjects: In a first cross-sectional study, we used data of 7380 Japanese women aged 14-83 years [body mass index (BMI): 22.6 +/- 3.7 kg/m(2)] at baseline. Among the participants, we used data of 54 women (BMI: 25.9 +/- 3.9 kg/m(2)) for a 5-month follow-up study., Measurements: Body fat percentage was evaluated by ADP and BI, and body fat (kg) and lean body mass (kg) were calculated. Anthropometric parameters, such as height, weight, BMI, waist circumference, hip circumference and waist hip ratio, were also measured. In a second longitudinal study, they were also investigated before and after the study., Results: In a first cross-sectional study, body fat percentage was 31.2 +/- 7.0% in ADP and 25.7 +/- 6.8% in BI. A significant relationship was observed between ADP and BI (r = 0.761, p < 0.01). In a second longitudinal study, body weight was significantly reduced. There were significant method (ADP vs. BI) and time (pre and post) effects but no interactions in assessing body fat percentage. There was a significant relationship between ADP and BI in body fat percentage, body fat and lean body mass. Delta body fat percentage (r = 0.386, p < 0.01) and delta body fat (r = 0.556, p < 0.01) measured by ADP were weakly correlated with those measured by BI. However, delta lean body mass measured by ADP was not correlated with that measured by BI., Conclusion: There was a discrepancy between ADP and BI for assessing body composition changes in Japanese women. ADP is preferentially recommended for evaluating body composition.

Aim: To investigate the link between serum leptin concentrations and exercise., Design: Cross-sectional and longitudinal studies of an exercise intervention., Subjects: 110 Japanese overweight men aged 32-59 years were recruited. At baseline, the average body mass index (BMI) was 28.5 +/- 2.5 kg/m2. From this group, we used data of 36 overweight men (BMI, 28.9 +/- 2.3) for a 1-year exercise programme., Measurements: Leptin was measured at baseline and after 1 year. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters, aerobic exercise level, muscle strength and flexibility were also investigated at baseline and after 1 year., Results: In the first analysis, using cross-sectional data, leptin was significantly correlated with total body fat (r = 0.760, p < 0.01), V (r = 0.383, p < 0.01) and S (r = 0.617, p < 0.01) areas. In the second analysis, using longitudinal data, leptin was significantly reduced after 1 year (pre 6.7 +/- 4.0 ng/ml vs. post 5.1 +/- 3.1 ng/ml, p < 0.01). Results showed that steps per day were increased, and aerobic exercise level, weight-bearing index (WBI) and insulin resistance were significantly improved. Although, there was a positive correlation between Delta leptin(positive changes in leptin after 1 year) and anthropometric measurements such as Delta body weight, Delta BMI and Delta body fat, leptin/body weight, leptin/BMI and leptin/body fat ratios were significantly reduced during exercise intervention., Conclusion: The present study indicated exercise significantly lowers serum leptin concentrations, and thus it may improve the leptin resistance observed in overweight Japanese men., (Copyright 2004 Blackwell Publishing Ltd)

Objective: To investigate the link between a reduction in blood pressure (BP) and daily exercise., Design: Cross-sectional and longitudinal clinical intervention study with exercise education., Subjects: 43 overweight Japanese men aged 32-59 years (BMI, 29.0+/-2.3 kg/m2) at baseline. Among the participants, a randomly selected 23 overweight men (BMI, 28.5+/-1.7) were further enrolled into the 10 months exercise program., Measurements: BP was measured every week and steps per day were also recorded every day throughout the observation period. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical level, at before, 5 months and after intervention. Anthropometric parameters were also measured at same point. Aerobic exercise level, muscle strength, flexibility and calorie intake and insulin resistance (HOMA index) were investigated at before and after the study., Results: In a cross sectional analysis, systolic BP (SBP) and diastolic BP (DBP) were significantly correlated with body composition. In a second longitudinal analysis, SBP was significantly reduced at 2 months and DBP was also reduced at 3 months, and almost maintained until the end of the observation period. Increasing daily walking was observed in 3 months and maintained until 10 months. Body composition, aerobic exercise level, muscle strength, flexibility and insulin resistance were significantly improved. There was positive correlation between DeltaDBP and Deltavisceral fat area (1-5, 5-10, 1-10 months). By stepwise multiple regression analysis, only Deltavisceral fat area was independently related to DeltaDBP at a significant level (1-10 months: DeltaDBP=-0.608+0.105Deltavisceral fat area, r2=0.227, P=0.0334)., Conclusion: The present study indicated daily exercise lowers BP and visceral fat area is the critical factor for BP change.

Objective: To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT)., Design: Cross-sectional and longitudinal clinical intervention study with exercise education., Subjects: In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program., Measurements: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months., Results: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels., Conclusion: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.

Background: Prescription of aerobic exercise for obese subjects with mild hypertension in clinical practice remains to be investigated., Methods: Forty-one Japanese obese males with hypertension were enrolled and compared with 41 age-and sex-matched obese subjects without hypertension and control subjects. In addition, 25 obese subjects with or without hypertension participated in a one-year follow up study. They were instructed to keep their low exercise intensity and record their daily walking. Before and after exercise prescription, body composition, blood pressure and aerobic exercise level were evaluated. Ventilatory threshold (VT) was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption (VO2), work rate (WR), heart rate (HR), deltaHR, %HR max, %HR reserve and rate of perceived exertion (RPE) were measured at VT., Results: At VT, obese subjects with hypertension had significantly lower VO2 (13.5 +/- 2.1 mL/kg/min) and WR (75.1 +/- 16.5W) than control subjects (VO2, 18.1 +/- 5.7; WR, 92.0 +/- 32.4). %HR reserve was also significantly lower compared with control subjects, while %HR max, was not different. RPE was also similar among the 3 groups. By prescribed low-grade exercise during one-year follow-up study, not only body composition but also blood pressure at rest was improved in obese subjects with and without hypertension., Conclusions: Our results indicated reduced exercise capacity in Japanese obese males. Exercise intensity of 60%HR max, 30%HR reserve and RPE 12 is recommended in obese subjects with hypertension as well as obese subjects without hypertension.

Objective: It is known that the accumulation of abdominal fat is one of the risk factors for atherosclerosis. Although exercise is commonly prescribed to reduce body weight, the efficacy of low intensity exercise for the reduction of abdominal visceral adipose tissue remains to be investigated., Research Design and Methods: Thirty one obese Japanese males (body mass index (BMI) > or = 25) ranging in age from 32 to 59, participated in a 1-year follow up study and they were instructed to have a modest increase in daily activity and record their daily walking. Before and after exercise prescription, body composition, blood pressure, physical fitness i.e. aerobic exercise level, muscle strength and flexibility were recorded. Insulin resistance was evaluated using a homeostasis model assessment, the HOMA index., Results: HOMA index, parameters of body composition, blood pressure, triglyceride and HDL cholesterol were significantly improved. The aerobic exercise level, leg strength, weight-bearing index (leg strength/body weight) and the steps taken per day were significantly increased. By stepwise multiple regression analysis, Delta visceral adipose tissue area was the major determinant for Delta HOMA index. (Delta HOMA index=-0.386+0.016 Delta visceral adipose tissue area, r2=0.267, P<0.01). Exercise capacity and calorie intake were not significantly related to Delta visceral adipose tissue area, while Delta steps per day was significantly correlated with Delta visceral adipose tissue area (Delta visceral adipose tissue area=-21.363-0.004 Delta steps per day, r2=0.184, P=0.0326)., Conclusions: Taken together, intra-abdominal visceral adipose tissue is critically involved in insulin resistance and daily walking rather than improvement of exercise capacity correlated with the reduction of visceral adipose tissue in obese Japanese males.

Purpose: We developed a one-year exercise program based on evaluation of life style and physical fitness and investigated its efficacy., Subjects and Methods: Sixty one Japanese males (30 < or = age < 59, body mass index: BMI > or = 26.4 kg/m2) were enrolled in the stady. The exercise program consisted of four sections: (1) Preparation for preventing injury; (2) Increase of daily activity; (3) Enjoying exercise; (4) Preparation and practice of individual-based on a exercise program. The subjects visited Okayama Southern Institute of Health and were being monitored weekly for one-year. They were instructed to check daily steps every day and increase daily walking to at least 1000 steps more than the daily walk at baseline. Before and after one-year follow up study, we evaluated life style and physical fitness in terms of body composition, aerobic exercise level, muscle strength and flexibility., Results: The continuation rate for the program was 66%. Body weight (pre 81.5 +/- 7.4 kg vs post 78.6 +/- 7.3 kg), body fat percentage (pre 30.3 +/- 4.1% vs post 28.4 +/- 5.0%) and waist hip ratio (pre 0.95 +/- 0.04 vs post 0.92 +/- 0.04) were significantly reduced. Aerobic exercise level and muscle strength were increased. Regarding volition for exercise, execution, continuation and steps per day were also improved., Conclusion: Regular exercise at an institution (once a week) and change in daily life style may play critical role in reducing body weight. This new program proved quite useful for Japanese obese males.

Objective: To establish an effective exercise prescription, the exercise capacity of obese subjects was investigated., Methods: In 71 male obese (body mass index: BMI > or = 26.4) Japanese, aged 26-77 years, the body composition and physical fitness such as aerobic exercise level, muscle strength and flexibility were determined and compared with those of age- and sex-matched 71 borderline (24.2 < or = BMI < 26.4) and 71 normal Japanese men (19.8 < or = BMI < 24.2). The relationship between body composition and other parameters was evaluated in obese subjects., Results: In obese subjects, body weight, BMI, body fat percentage, waist hip ratio, and skinfold thickness were higher than those of borderline and normal subjects. Lower aerobic exercise level and weight bearing index (WBI) were noted in obese subjects. There was a negative correlation between waist hip ratio and aerobic exercise level (oxygen uptake at ventilatory threshold) (r = -0.509, P < 0.01) and also between waist hip ratio and WBI (r = -0.315, P < 0.01)., Conclusions: Lower physical fitness is considered to be a general characteristic of male obese Japanese, and the accumulation of visceral adipose tissue might affect exercise capacity.

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index > or =26.4) subjects, aged 20-79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist-hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist-hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist-hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle.

OBJECTIVE: To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: One-hundred and twelve Japanese overweight men aged 30-59 y (body mass index (BMI) 28.4 ± 2.5 kg/m²) and 33 normal-weight men aged 30-39 y (BMI 22.1 ± l.5 kg/m²) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8 ± 2.8) were further enrolled into a 1 y exercise program. MEASUREMENTS: Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y. RESULTS: In 112 overweight subjects at baseline, insulin (10.5 ± 5.0 µU/ml) and leptin (6.4 ± 3.7 ng/ml) significantly correlated with both V (r = 0.260, P = 0.0073; r = 0.410, P < 0.0001) and S areas (r = 0.377, P < 0.0001; r = 0.613, P < 0.0001), respectively. IGF-I (156.8 ± 48.7 µU/ml) significantly and negatively correlated with V area (r = -0.242, P = 0.0125) and age (r = -0.192, P = 0.0480). In normal-weight men aged 30-39 y (n = 33) and age-matched subjects (n = 30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r = -0.467, P < 0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224 ± 2781 to 7898 ± 4141 steps/day) and reduction of BMI (28.8 ± 2.8 to 27.7 ± 2.9). ΔIGF-I significantly correlated with ΔV area (r = -0.432, P = 0.0009) but not with ΔS area or ΔBMI. CONCLUSION: The present study indicated a... [ABSTRACT FROM AUTHOR]