| 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 |
Metabolic syndrome, which clusters glucose intolerance, hypertension and dyslipidemia in each individual, is a common cause of atherosclerotic vascular disease. People with the metabolic syndrome often accompanies with insulin resistance. The molecular basis of the metabolic syndrome, however, has not been elucidated. We discovered a novel adipocyte-derived factor named adiponectin. In this project, we investigated the role of adiponectin in the pathogenesis of the metabolic syndrome. 1)We generated mice lacking adiponectin. Adiponectin knockout mice (KO) showed severer insulin resistance under high fat, high sucrose diet, and severer neointimal thickening by vascular injury compared to wild type mice. KO also showed impaired endothelium-dependent vascular relaxation, and slightly elevated blood pressure level. 2)By the screening of mutations in the adiponectin gene, we identified a missense mutation with low plasma adiponectin level. The subjects carrying this mutation frequently accompanied glucose intolerance, hypertension and dyslipidemia. The prevalence of this mutation was higher in the patients with coronary artery disease than controls. 3)Overexpression of adiponectin in apoE KO mice prevented the formation of fatty streak lesion. 4)Pima indians with high plasma adiponectin level had negative risk for the later onset of type 2 diabetes. Among the subjects with renal insufficiency, people with high plasma adiponectin level at baseline showed lower incidence of the cardiac events, These results indicated adiponectin is a bi-functional molecule having insulin-sensitizing and anti-atherogenic activities independently. The reduction of plasma adiponectin by overnutrion may play an important role in the development of the metabolic syndrome.
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