| Project/Area Number |
20390085
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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 | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Juntendo University |
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Principal Investigator |
SHIRASAWA Takuji Juntendo University, 大学院・医学研究科, 客員教授 (80226323)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Takahiko 地方独立法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究員 (40301791)
TOMITA Kengo 慶応義塾大学, 医学部, 助教 (50317129)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
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| Keywords | 加齢 / 酸化ストレス / 脂肪肝 / NASH / モデルマウス / SOD / 肥満 / レプチン |
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| Research Abstract |
To investigate pathological role of oxidative stress on nonalcoholic steatohepatitis (NASH), we used CuZn-SOD-deficient mice, which developed spontaneous fatty liver with increased oxidative stress. Although methionine and choline-deficient (MCD) diet induced NASH-like pathologies in wild-type mice, CuZn-SOD-deficient mice failed to show typical hepatic injuries, suggesting that CuZn-SOD deficiency prevented from MCD-diet induced by hepatic stress. Furthermore, we crossbred CuZn-SOD-deficient mice with ob/ob mice to investigate pathological role of obesity on hepatic CuZn-SOD deficiency. Interestingly, double mutant mice also failed to show apparent hepatic abnormalities, suggesting that CuZn-SOD deficiency does not accelerate hepatic pathologies induced by impaired leptin signaling and obesity.
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