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...

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