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Obesity is a complex phenotype resulting from the combined effects of genes, behavioural and lifestyle factors, and their interactions [1]. The associations between obesity and increased risk of morbidity and mortality are well documented [2]; however, distribution of body fat is also of importance [3]. A syndrome with a clustering of multiple risk factors for coronary atherosclerosis has been described and defined by Reaven [4] as syndrome X; by Kaplan [5] as the deadly quartet; and by Matsuzawa et al. [6] as visceral fat obesity, which is more strongly associated with metabolic and cardiovascular diseases than subcutaneous fat obesity [7,8]. From clinical and basic experiments, the imbalance of sex hormones [9], aging [10], excessive intake of sucrose [11] and lack of physical exercise [10] have been suggested to be major factors for visceral fat accumulation. However, it is not known whether a major gene exists which promotes visceral fat accumulation, although Bouchard et al. [12] demonstrated six times more variation between twin pairs than within twin pairs for an Diabetologia (1997) Summary We investigated whether the polymorphism of the b 3 -adrenergic receptor (b 3 -AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects , n = 48) women than in women homozygous for the Trp 64 Trp (121 ± 46 cm 2 , n = 77) genotype (p < 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp 64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p < 0.004). Moreover, homozygous carriers of the Arg 64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp 64 allele. Some of these differences were also observed between heterozygous Trp 64 Arg and homozygous Trp 64 Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the b 3 -AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome. [Diabetologia (1997) 40: 200-204]

Objectives. To assess the association of trunk and leg fat mass (FM) and leg lean tissue mass (LTM) with conventional cardiovascular risk factors. Design. Cross-sectional study. Setting and subjects. We studied 1249 men and 3007 women (age 20-79 years) who attended a research institute for a health checkup between October 1995 and February 2004. Main outcome measures. Body mass index, waist circumference (WC), hip circumference (HC), systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides, glucose and haemoglobin A 1C were measured. Trunk FM, leg FM and leg LTM were obtained by dual-energy X-ray absorptiometry. We evaluated the associations between the indices for regional body composition and cardiovascular risk factors, which included hypertension, hypercholesterolaemia, hypo-HDL cholesterolaemia, hypertriglyceridaemia, dyslipidaemia and diabetes mellitus. Results. Increase in WC and HC respectively showed increase and decrease in odds ratios of cardiovascular risk factors. Increase in trunk FM by 1 kg significantly increased the risk of the cardiovascular risk factors with the odds ratios ranging between 1.11 and 1.45. Increase in leg FM by 1 kg significantly decreased the risk with the odds ratios ranging between 0.52 and 0.90, except for the nonsignificant results for hypercholesterolaemia and hypo-HDL cholesterolaemia in men. Odds ratios of 1 kg increase in leg LTM were only significant for dyslipidaemia in men and hypercholesterolaemia in women (both 0.93). Conclusions. WC and HC showed opposite and independent associations with cardiovascular risk factors. The favourable association of HC was mainly attributable to that of leg FM.

OBJECTIVE: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5 kg/m 2 (265 males and 741 females, age 21-69 y). MEASUREMENTS: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FM trunk /FM legs ) were obtained by dual-energy X-ray absorptiometry. RESULTS: WC, WHR, %FM and FM trunk /FM legs were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FM trunk /FM legs to show the strongest correlations. For %FM and FM trunk /FM legs in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.