| Co-Investigator(Kenkyū-buntansha) |
KIHARA Shinji Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20332736)
NAKAMURA Tadashi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90252668)
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| Research Abstract |
The metabolic syndrome is a cluster of impaired glucose tolerance, dyslipidemia and hypertension, and is a common basis of type 2 diabetes and atherosclerotic vascular diseases. The molecular basis of the metabolic syndrome has not been elucidated. We postulated the accumulation of intra-abdominal visceral fat caused by overnutrion locates upstream of the metabolic syndrome, and analyzed the expressed gene-profile of the visceral fat Though the analyzes, we identified a novel adipocyte-derived factor named adiponectin. Adiponectin is an adrpose-specific plasma protein composed of fiburaous collagen-like domain and globular complement-like domain. We demonstrated that this protein has potential anti-atherogenic properties including suppression of adhesion molecules in endothelial cells and cytokine-production in macrophages, and the plasma concentration of adiponectin decreased in the subjects with viscera fat accumulation. In the present study, we investigated the role of adiponectin in insulin resistance. Plasma concentration of adiponectin decreased in the subjects with type 2 diabetes. Euglycemic hyperinsulinemic studies revealed plasma adiponectin levels closely correlated with insulin sensitivity. In rhesus monkeys, which develop obesity and type 2 diabetes under ad libtum, plasma adiponectin concentrations decreased soon after the development of obesity, and proceeded the onset of insulin resistance Expression and plasma levels of adiponectin were increased by PPARg ligands, which are known as insulin-sensitizing agents. Taken together with former observations, our present results suggest that adiponectin affects both vascular function and insulin sensitivity, and hypoadiponectinemia caused by visceral fat acculation may play a key role in the development of the metabolic syndrome.
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