Molecular mechanism of BDNF as a agent that circumvents leptin resistance
| Project/Area Number |
13557089
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Endocrinology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OGAWA Yoshihiro Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70291424)
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| Co-Investigator(Kenkyū-buntansha) |
TAIJI Mutsuo Sumitomo Pharmaceuticals, Research Scientist, 創薬第二研究所, 主任研究員
HOSODA Kiminori Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (40271598)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2002: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | leptin resistance / BDNF / obesity / diabetes / DIO mice / KKA^y mice / transgenic mice / KKA^yマウス / 高脂肪食負荷 / レプチン |
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| Research Abstract |
In this study, we investigated whether or not brain-derived neurotrophic factor (BDNF) acts as an antiobesity and antidiabetic agent that can circumvent leptin resistance. We demonstrated that BDNF is effective in two different models of leptin resistance; an acquired model or C57BL/6J mice rendered obese by consumption of high-fat diet for 4 months (diet-induced obesity (DIO) mice) and a genetic model or lethal yellow agouti mice (KKA^y mice). Intraperitoneal (IP) administration of BDNF (10 mg/kg × 2) reduced significantly cumulative food intake of DIO mice over 24 h, whereas they were unresponsive to IP administration of leptin (10 mg/kg × 2). The antiobesity effect of BDNF was marginal in mice fed standard diet. IP injection of recombinant leptin caused a marked reduction of cumulative food intake in mice fed standard diet over 24. We next examined the effect of repetitive administration of BDNF (10 mg/kg/day for 6 days) in DIO mice and oral glucose tolerance test (OGTT) was conducted after the last administration. The area under curve (AUC) of blood glucose of BDNF-treated DIO mice was significantly lower than vehicle-treated DIO mice during OGTT (P < 0.01). We also observed that BDNF is effective in improving obesity and diabetes of KKA^y mice. Very recently, we have produced transgenic mice overexpressing BDNF under the control of the liver-specific serum amyloid P component P promoter and found that they exhibit reduced food intake and body weight relative to nontransgenic littermates, when fed either standard or high-fat diet. Collectively, these observations suggest that BDNF may be therapeutically used in the treatment of leptin-resistant obesity and diabetes.
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Report
(3 results)
Research Products
(16 results)
