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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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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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 / SHRSP5/Dmcr / コレステロール / コール酸 / ケノデオキシコール酸 / デオキシコール酸 / リトコール酸 / 線維症進展 / 肝線維症 / M30抗原 / 壊死 / カスパーゼ3/7 / 高脂肪食 / SHRSP / Wistar Kyoto / 脂肪感 / 炎症 / 性差 |
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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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Report
(4 results)
Research Products
(38 results)
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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
Dig Dis Sci
Volume: -
Issue: 7
Pages: 1490-1501
DOI
Related Report
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)
Issue: 18-19
Pages: 673-680
DOI
Related Report
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)
Issue: 8
Pages: 2212-22
DOI
Related Report
Peer Reviewed
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[Presentation] Chenodeoxycholic acid and total glycine-conjugated bile acids correlate to steatohepatitis and fibrosis caused by a high fat-cholesterol diet in rats2013
Author(s)
Xiaofang Jia, Yudai Suzuki, Hisao Naito, Husna Yetti, Kazuya Kitamori, Yumi Hayashi, Rina Kaneko, Mina Nomura, Yukio Yamori, Akira Ishii, Tamie Nakajima
Organizer
第83回日本衛生学会学術総会
Place of Presentation
金沢大学（石川県）
Related Report
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