2007 Fiscal Year Final Research Report Summary
Preventive effects of resveratrol on obesity-associated thrombosis and insulin resistance
| Project/Area Number |
17590988
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
IHARA Hayato Hamamatsu University School of Medicine, Dept. Physiol, Assistant Professor (00223298)
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| Co-Investigator(Kenkyū-buntansha) |
URANO Tetsumei Hamamatsu Univ. Sch. Med, Dept. Physiol, Professor (50193967)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Resveratrol / Adipocyte / Resistin / Phasminogen Activator Inhibitor 1 (PAI-1) / Obese mice / 抗酸化物質 |
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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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Description
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Author(s)
Yamashita, T., Dai, Q., Ihara, H., Suzuki, Y., Mogami, H., Koide, T., Castellino, F.J, Urano, T
Organizer
18th Congress on Fibrinolysis, Proteolysis
Place of Presentation
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Year and Date
20060800
Description
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