2013 Fiscal Year Final Research Report
Molecular mechanism for prevention of high-fat and -cholesterol-induced fibrotic steatohepatitis and development of the non-invasive biomarker
| Project/Area Number |
23390161
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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 |
Hygiene
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| Research Institution | Chubu University (2012-2013)
Nagoya University (2011) |
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Principal Investigator |
NASU Tamie 中部大学, 生命健康科学部, 教授 (10020794)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Akira 名古屋大学, 医学系研究科, 教授 (30252175)
NAITO Hisao 名古屋大学, 医学系研究科, 助教 (90547556)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | SHRSP5/Dmcrラット / 高脂肪・高コレステロール食 / 肝炎 / 線維化 / エイコサペンタエン酸 / ウルソデオキシコール酸 / バイオマーカー / 胆汁酸 |
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| Research Abstract |
High-fat and-cholesterol diet (HFC) induced hepatic fibrosis greater in SHRSP5/Dmcr than SHRSP. This was due to greater suppression of UGT, CAR and PXR in the former than the latter. The fibrosis area was greater in males than females. The UGT activity and expressions of CAR and PXR, were not suppressed by HFC diet in females, while significantly suppressed in males, suggesting this enzyme and its nuclea receptors excreting bile acid may be one of important role in the sex differences in the histopathological finding. EPA prevented inflammation by inhibiting increase of p65/p50, however, did not influence fibrosis development.
HFC diet mainly induced necrosis in the liver by decrease in caspase 3/7 activity. Serum K18Asp396 levels were positively correlated with hepatocyte necrosis and fibrosis, suggesting that the levels may be a good noninvasive biomarker of these findingss. According to HFC-diet feeding, ratio of cholic acid/chenodeoxycholic acid (CDCA)significantly decreased.
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[Journal Article] A Possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model2014
Author(s)
Jia X, Suzuki Y, Naito H, Yetti H, Kitamori K, Hayashi Y, Kaneko R, Nomura M, Yamori Y, Zaitsu K, Kato M, Ishii A, Nakajima T
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Journal Title
DOI
Peer Reviewed
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[Journal Article] High-fat-cholesterol diet-induced mainly necrosis fibrotic steatohepatities rats by suppressing caspase activity2013
Author(s)
Yetti H, Naito H, Jia X, Shindo M, Taki H, Tamada H, Kitamori K, Hayashi Y, Ikeda K, Yamori Y, Nakajima T
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Journal Title
Life Sciences
Volume: No4.93(18-19)
Pages: 673-680
DOI
Peer Reviewed
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[Journal Article] Dysregulated bile acid synthesis, metabolism and excretion in a high fat-cholesterol diet-induced fibrotic steatohepatitis in rats2013
Author(s)
Jia X, Naito H, Yetti H, Tamada H, Kitamori K, Hayashi Y, Wang D, Yanagiba Y, Wang J, Ikeda K, Yamori Y, Nakajima T
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Journal Title
Digestive Diseases Sciences
Volume: 58(8)
Pages: 2212-22
DOI
Peer Reviewed
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[Journal Article] The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model2012
Author(s)
Jia X, Naito H, Yetti H, Tamada H, Kitamori K, Hayashi Y, Yamagishi N, Wang D, Yanagiba Y, Ito Y, Wang J, Tanaka N, Ikeda K, Yamori Y, Nakajima T
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Journal Title
Life Sci
Volume: 90(23-24)
Pages: 934-943
DOI
Peer Reviewed
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[Journal Article] Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat2012
Author(s)
Moriya T, Kitamori K, Naito H, Yanagiba Y, Ito Y, Yamagishi N, Tamada H, Jia XF, Tsuchikura S, Ikeda K, Yamori Y, Nakajima T
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Journal Title
Environ Health Prev Med
Volume: 17(6)
Pages: 444-456
DOI
Peer Reviewed
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[Journal Article] Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr2012
Author(s)
Kitamori K, Naito H, Tamada H, Kobayashi M, Miyazawa D, Yasui Y, Sonoda K, Tsuchikura S, Yasui N, Ikeda K, Moriya T, Yamori Y, Nakajima T
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Journal Title
Environ Health Prev Med
Volume: 17(3)
Pages: 173-182
DOI
Peer Reviewed
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