| Budget Amount *help |
¥115,200,000 (Direct Cost: ¥115,200,000)
Fiscal Year 2007: ¥21,600,000 (Direct Cost: ¥21,600,000)
Fiscal Year 2006: ¥21,600,000 (Direct Cost: ¥21,600,000)
Fiscal Year 2005: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2004: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2003: ¥24,000,000 (Direct Cost: ¥24,000,000)
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| Research Abstract |
Metabolic syndrome is the common cause of atherosclerotic cardiovascular diseases. We have reported that visceral fat accumulation is the key feature of thepathophysiology, and found adiponectin and aquaporin adipose from human adipose tissue cDNA library.
Plasma adiponectin levels positively correlated to insulin sensitivity and endothelium-dependent vasodilation, and negatively correlated with visceral fat mass. Hypoadiponectinemia was an independent risk for type 2 diabetes, hypertension and coronary artery disease. Moreover, the subjects with genetic hypoadiponectinemia had high susceptibility to the metabolic syndrome. The adiponectin deficient mice exhibited diet-induced diabetes mellitus or hypertension, pressure overload-stimulated adverse cardiac hypertrophy, ischemia-reperfusion injury-induced increased myocardial infarct size, and glomerular hyperfiltration-induced exacerbation of urinary albumin and renal fibrosis. Adiponectin supplementation restored these abnormalities, in
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dicating that adiponectin insufficiency involves obesity-linked diabetes, hypertension, kidney disease, and cardiovascular diseases. In cultures of vascular endothelial cells and cardiac myocytes, adiponectin augmented AMP-activated protein kinase and suppressed the cell death. In cultures of macrophages, adiponectin treatment suppressed foam cell transformation, and increased tissue inhibitor of metalloproteinase-1 levels through enhanced interleukin-10 secretion. These findings suggest that adiponectin protect systemic vascular system from adverse nutritional, inflammatory, and mechanical stress overload. In addition, we investigated the role of aquaporin adipose, the glycerol channel in adipocyte. Aquaporin adipose-deficient mice showed a disrupted increase of plasma glycerol and rapid reduction of plasma glucose during prolonged fasting. The fat mass and adipocyte size were increased significantly in aquaporin adipose-deficient mice compared with control mice. Aquaporin adipose disruption caused the enhanced glycerol kinase enzymatic activity in adipocytes. These findings suggest that aquaporin adipose dysfunction causes hypoglycemia, accelerated adipose triglycerides synthesis, and, finally, develops obesity.
The measurement of plasma adiponectin level will be clinically useful to evaluate diabetic and atherosclerotic disease risk. The adipocyte expressed genes including adiponectin and aquaporin adipose can be target molecules for preventing life style-mediated metabolic and cardiovascular diseases. Less
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