| Project/Area Number |
26282191
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SHODA JUNICHI 筑波大学, 医学医療系, 教授 (90241827)
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| Co-Investigator(Kenkyū-buntansha) |
柳川 徹 筑波大学, 医学医療系, 准教授 (10312852)
酒井 俊 筑波大学, 医学医療系, 講師 (30282362)
磯辺 智範 筑波大学, 医学医療系, 准教授 (70383643)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 肥満 / 脂肪性肝炎 / 転写因子 / 酸化ストレス / エンドトキシン / 遺伝子改変マウス / 生活習慣病 / 非アルコール性脂肪性肝炎 / 腸内細菌 / インスリン抵抗性 / 遺伝子レスキューマウス |
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| Outline of Final Research Achievements |
p62:Nrf2 double knockout mice (DKO) fed with normal diet develop spontaneous NASH in association with mature-onset hyperphagic obesity. Therefore, to elucidate the onset mechanism of NASH, we focused interests on the intestines and Kupffer cells. In the analysis of intestinal microflora, the number of gram-negative bacteria species was increased in DKO and the serum and fecal LPS concentrations were also increased. The intestinal permeability was increased in Nrf2-KO mice and DKO. The inflammatory cytokine production was increased in the Kupffer cells. It is likely that the onset mechanism of NASH is attributed to an increase in gram-negative bacteria species due to p62 deficiency and a weakness of intestinal barrier function due to Nrf2 defeciency, which in turn let an increased influx of LPS into the liver.
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