| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Resveratrol (3, 5, 4'-trihydroxystilbene) was isolated from the roots of polygonun cuspidatum as a traditional Chinese and Japanese medicine, kou-jou-kon in 1960s. Now, it has been shown that resveratrol can prevent or suppress the progression of a wide variety of illnesses, including cancer, cardiovascular disease and ischemic injuries. It also enhances stress resistance and extends the life-spans of various organisms from yeast to vertebrates. We hypothesized that resveratrol have preventive effects on obesity-associated insulin resistance and cardiovascular disease: by suppressing the gene expression of adipocyte-derived mediator, resistin and/or a risk factor of thrombosis, PAI-1. Treatment of 3T3-L1 cells with resveratrol attenuated adipocyte differentiation, which resulted in a dramatic decrease in resistin mRNA levels as well as resistin secreted into the culture medium. Transient transfection experiments with resistin promoter/luciferase reporter revealed that resveratrol reduced transcriptional activity of the resistin gene in a dose-dependent manner. In contrast, the PAI-1 gene expression was enhanced 2-fold within 24 hr after resveratrol treatments. Furthermore, we investigated the effects of resveratrol administration in vivo on the plasma levels of resistin and PAI-1 and also on the gene expressions of these molecules in adipose tissue. Long-term (2 weeks) administration of resveratrol (50 mg/kg B.W.) in ob/ob mice significantly reduced plasma levels of resistin, but not PAI-1. Real-time PCR experiments revealed that resistin mRNA levels in adipose tissue were down-regulated by the treatments with resveratrol. In contrast, PAI-1 mRNA levels was increased under the same condition. These results indicate that the resistin gene expression is down-regulated by resveratrol in vivo and in vitro and that resveratrol has a beneficial effect for obesity-associated insulin resistance.
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