The authors estimated abdominal fat distribution on the basis of measurements at computed tomography (CT). The attenuation range for fat tissue was defined as the interval within the mean plus or minus 2 SDs considered to be individual variation. Fat areas found with this method were closely correlated with those obtained by means of the computed planimetric method or with a fixed attenuation range from -190 to -30 HU as the standard of reference. Although the average CT numbers obtained with different scanners were distributed widely, the calculated fat areas were almost identical. This method might be a practical and standardized method at CT.

The presence of obesity increases the risk of thrombotic vascular diseases. The role of fat accumulation and its effect on plasminogen activator inhibitor-1 (PAI-1) levels was investigated in humans and animals. Plasma PAI-1 levels were closely correlated with visceral fat area but not with subcutaneous fat area in human subjects. PAI-1 mRNA was detected in both types of fat tissue in obese rats but increased only in visceral fat during the development of obesity. These data suggest that an enhanced expression of the PAI-1 gene in visceral fat may increase plasma levels and may have a role in the development of vascular disease in visceral obesity.

Objectives-A low level of high-density lipoprotein (HDL) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events. However, the physiological regulation of plasma HDL levels has not been completely defined. Current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to HDL metabolism. Methods and Results-Angptl3-deficient mice showed low plasma HDL cholesterol and HDL phospholipid (PL), and which were increased by ANGPTL3 supplementation via adenovirus. In vitro, ANGPTL3 inhibited the phospholipase activity of endothelial lipase (EL), which hydrolyzes HDL-PL and hence decreases plasma HDL levels, through a putative heparin-binding site in the N-terminal domain of ANGPTL3. Post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angptl3-deficient mice. Furthermore, we established an ELISA system for human ANGPTL3 and found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects. Key Words: angptl3 Ⅲ high density lipoprotein Ⅲ endothelial lipase Ⅲ phospholipase Ⅲ triglyceride P lasma concentrations of high-density lipoprotein (HDL) cholesterol are inversely correlated with the risk of atherosclerotic cardiovascular disease. 1 HDL cholesterol levels are low in patients with metabolic disorders, such as obesity, insulin resistance, and diabetes. 2,3 However, the genetic and metabolic factors that regulate HDL metabolism remain to be elucidated. Recently, endothelial lipase (EL) has been recognized as one factor that influences HDL metabolism. EL was originally discovered as a member of the family of triglyceride (TG)-lipases together with lipoprotein lipase (LPL) and hepatic lipase (HL). In contrast to LPL or HL, however, EL has relatively lower triglyceride lipase activity and substantially higher phospholipid lipase activity and can hydrolyze HDL phospholipids (PL). 4 Overexpression of EL in mice resulted in reduced plasma HDL levels and EL knockout mice showed significant increase in HDL levels, [5][6][7] indicating that EL regulates HDL metabolism. Conclusions-Angptl3In the colony of KK mice, characterized by obesity, diabetes mellitus, and hypertriglyceridemia, we recently identified a mutant subgroup of KK/Snk mice with low plasma TG levels despite maintaining the phenotype of obesity and diabetes. Genetic mapping and positional cloning identified the gene of angiopoietin-like protein 3 (Angptl3), which was mutated in the KK/Snk mice. The Angptl3 gene in KK/Snk mice contained a 4-bp nucleotide insertion in exon 6, which caused a premature stop codon attributable to a frameshift, leading to a lack of production of the protein. 8 Angptl3 mRNA is expressed exclusively in the livers of humans and mice. ANGPTL3 protein contains a signal sequence of 18 amino acids at the N terminus, followed b...

No abstract

Variations 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) C 30 kg/m 2 ] and normalweight control subjects (n = 1,527, BMI \ 25 kg/m 2 ).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. rs1558902 genotype. Thus, the SNPs in the FTO gene were found to be associated with obesity, i.e., severe obesity, in the Japanese.

Abstract. Shinohara E, Kihara

The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6±3.1; average age, 50±ll years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53±0.33 versus 0.29±0.12, p<0.01). Significant correlations between the ratio of intra-abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r=0.62, p< 0.001) and diastolic blood pressure (r=0.53, p< 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity. (Hypertension 1990;16:484-490) I t has been noted that the incidence of circulatory and metabolic complications among comparably obese subjects differs depending on their body habitus.1 We have developed a method to estimate fat distribution using computed tomography (CT) scan, which clearly distinguishes between subcutaneous fat and intra-abdominal visceral fat 2 and have demonstrated a close correlation between intra-abdominal fat accumulation and metabolic disturbances.3 Further, using this method we reported that the accumulation of intra-abdominal visceral fat itself may reflect cardiac dysfunction and metabolic disorders better than subcutaneous fat. 4 -7 Therefore, we propose the existence of two types of obesity: visceral fat obesity, characterized by a pronounced accumulation of fat in the abdominal cavity, and subcutaneous fat obesity, From The Second Department of Internal Medicine, Osaka University Medical School, Fukushima-ku, Osaka, Japan.Presented in part at the 62nd Annual Scientific Sessions of the American Heart Association, New Orleans, Louisiana, November [13][14][15][16] 1989.Address for correspondence: Hideyuki Kanai, MD, The Second Department of Internal Medicine, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553, Japan.Received March 7,199O, accepted in revised form June 15,1990. characterized by an accumulation mainly in the subcutis (Figure 1). We also reported 8 that this classification is more useful than other classifications of fat distribution, 9 "16 including the waist-to-hip circum...

Based on the analysis of fat distribution by computed tomography (CT) scans, the classification scheme for obesity should include visceral fat obesity in which fat accumulationis predominant in the intra-abdominalcavity. Obese subjectsivith visceral fat accumulation more frequently demonstrateimpairment of glucose andlipid metabolism than those withsubcutaneous fat accumulation. Wehaveshownthatvisceralfat obesity is present in almost90% ofobesepatientswithischemicheart disease. Even in non-obese subj ects, visceral fat accumulation is correlatedwith glucose intolerance, hyperlipidemia and hypertension. Forty percent of non-obese subjects with coronary artery disease (CAD) had increased visceral fat. In non-obese subjects, visceral fat area assessed by abdominal CT at the level of the umbilicus correlates with metabolic risk factors, whereas in obese subjects the visceralfat area to subcutaneous fat area ratio provides a more significant correlation.From clinical and basic investigations, aging, sex hormones, excess intake of sucrose and lackof physical exercise have been suggested to be determinants for visceral fat accumulation. Since intra-abdominal fat (mesenteric andomentum fat) has beenshown to havehigh activities of bothlipogenesis and lipolysis,its accumulation can induce high levels offree fatty acids, a product of lipolysis, in portal circulation which go into the liver. Excess free fatty acids may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis.