Elucidation of the role of bile acids and short-chain fatty acids in the onset and progression of non-alcoholic steatohepatitis
Project/Area Number |
18K07069
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | The University of Tokushima |
Principal Investigator |
TSUNEYAMA Koichi 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10293341)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 非アルコール性脂肪肝炎 / 胆汁酸 / 短鎖脂肪酸 / ラマン顕微鏡 / 動物モデル / NASH / 肝細胞癌 / 質量分析 / 非アルコール性脂肪性肝炎 / イメージング質量分析 |
Outline of Final Research Achievements |
We succeeded in inducing characteristic fibrosis mimic to human non-alcoholic steatohepatitis in the liver by adding cholic acid to mice on a high-fat / high-cholesterol diet. We analyzed the lipid droplets accumulated in hepatocytes and the surrounding microenvironment with a Raman microscope or imaging mass spectrometry. It was clarified that specific lipids were associated with fibrosis through the activation of macrophages. In addition, various oligosaccharides were administered to TSOD mice spontaneously developing metabolic syndrome. As expected, oligosaccharide administration improved blood glucose level, urinary sugar, and liver histology. Oligosaccharides have positively affected intestinal bacterial flora, and improvement of short-chain fatty acids was identified. It has been suggested the possibility of dietary NASH prevention and treatment.
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Academic Significance and Societal Importance of the Research Achievements |
メタボリックシンドロームの肝表現型である非アルコール性脂肪肝炎(NASH)は患者数が急増している難治性疾患である。研究代表者は脂質と胆汁酸を交えた食によって、マウスにヒトと類似したNASH-線維化を誘導することに成功し、これらモデル動物を用いてNASHの線維化に異常脂質や胆汁酸が関与していることを明らかにした。さらに食の成分であるオリゴ糖の投与によって腸内環境の改善による短鎖脂肪酸のバランス是正が生じ、NASHの病態が改善することを見出した。本研究はNASHの発症進展や病態改善がいずれも食によってコントロールできる可能性を示したものであり、NASHの全容解明に有用な知見と考えられた。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] The challenges of primary biliary cholangitis: What is new and what needs to be done2019
Author(s)
Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Bowlus C, Carbone M, Chazouill O, et al.
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Journal Title
Journal of Autoimmunity
Volume: 105
Pages: 102328-102328
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Anti-drug Antibodies Against a Novel Humanized Anti-CD20 Antibody Impair Its Therapeutic Effect on Primary Biliary Cholangitis in Human CD20- and FcγR-Expressing Mice2018
Author(s)
Moritoki Y, Tsuneyama K, Nakamura Y, Kikuchi K, Shiota A, Ohsugi Y, Lian ZX, Zhang W, Yang GX, Ueki S, Takeda M, Omokawa A, Saga T, Saga A, Watanabe D, Miura M, Ueno Y, Leung PSC, Tanaka A, Gershwin ME, Hirokawa M.
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Journal Title
Frontiers in Immunology
Volume: 9
Pages: 2534-2534
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A fermented mixed tea made with camellia (Camellia japonica) and third-crop green tea leaves prevents nonalcoholic steatohepatitis in Sprague-Dawley rats fed a high-fat and high-cholesterol diet2018
Author(s)
Katsuhisa Omagari, Kazuhito Suruga, Akira Kyogoku, Satomi Nakamura, Ai Sakamoto, Shinta Nishioka, Mayuko Ichimura, Yuji Miyata, Koichi Tajima, Koichi Tsuneyama, Kazunari Tanaka
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Journal Title
Hepatobiliary Surgery and Nutrition
Volume: -
Issue: 3
Pages: 175-184
DOI
Related Report
Peer Reviewed / Open Access
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