Involvement of 12alpha-hydroxylated bile acids in the onset and aggravation of fatty liver
| Project/Area Number |
19H02900
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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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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
相沢 智康 北海道大学, 先端生命科学研究院, 教授 (40333596)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
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| Keywords | 胆汁酸 / 脂肪肝 / 12α水酸化胆汁酸 / bile acids / liver lipid accumulation |
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| Outline of Research at the Start |
非アルコール性脂肪肝疾患の頻度は年々増加しており、その発症には肝臓に脂質がたまることに加え、炎症・繊維化などが積み重なることで悪化していくと考えられています。過剰摂取で摂取エネルギーが増えると、コレステロールから生じる胆汁酸の一部が増加します。このタイプの胆汁酸が実験動物で肝臓の脂質蓄積を増やすこと、その時に肝臓での脂質合成の亢進が見られたことから、特定の胆汁酸が脂肪肝の発症に関わることが示唆されます。そこで、胆汁酸による肝臓での脂質蓄積の機構を明らかにする研究を行います。また、この脂肪肝は重篤な症状ではないため、このモデルを用いて脂肪肝の悪化に関わる要因を併せて検討します。
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| Outline of Final Research Achievements |
Fatty liver is associated with development of noncommunicable diseases. inflammation and fibrosis occur based on lipid accumulation in the development of fatty liver. Although a high-fat-fed experimental animals are a well-known fatty liver model, those animals frequently have both lipid accumulation and inflammation in the liver, and no reasonable model is reported to separate lipid accumulation and inflammation with fibrosis. We observed an enhancement of secretion of 12α-hydroxylated bile acids from the liver in response to dietary energy and those bile acids induces liver lipid accumulation without inflammation and fibrosis. Also, induction of inflammation was found to aggravate the symptom substantially. This can be used as a presymptomatic model of fatty liver.
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| Academic Significance and Societal Importance of the Research Achievements |
脂肪肝の発症モデルとして、炎症・繊維化を伴わない肝臓での脂質蓄積のみを呈するモデルを見出したことと、炎症を強制的に誘導させたときにはその症状が悪化するという単なる脂質蓄積に留まらない点を見出したことに学術的な意義があると考えられる。また、このモデルでは食事からのエネルギー摂取は通常のままで、肥満症状にはならない。健康診断などで見た目は肥満でなくても肝臓脂肪の蓄積が見られるヒトのモデルと考えることもでき、その後に起こりうる多様な疾患の予防において重要な観点を提示できた点は大きな成果と考えられる。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Dietary supplementation with okara and Bacillus coagulans lilac-01 improves hepatic lipid accumulation induced by cholic acids in rats2022
Author(s)
Lee Yeonmi, Tanaka Yasutake, Iwasaki Wakana, Yokoyama Fumika, Joe Ga-Hyun, Tsuji Misaki, Nose Takuma, Tada Koji, Hanai Taketo, Hori Shota, Shimizu Hidehisa, Minamida Kimiko, Miwa Kazunori, Ishizuka Satoshi
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Journal Title
Journal of Functional Foods
Volume: 90
Pages: 104991-104991
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum2021
Author(s)
Yoshitsugu Reika, Liu Hongxia, Kamo Yoshie, Takeuchi Akari, Joe Ga-Hyun, Tada Koji, Kikuchi Keidai, Fujii Nobuyuki, Kitta Shinri, Hori Shota, Takatsuki Manami, Iwaya Hitoshi, Tanaka Yasutake, Shimizu Hidehisa, Ishizuka Satoshi
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Journal Title
Scientific Reports
Volume: 11
Issue: 1
Pages: 12939-12939
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 12α-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats2020
Author(s)
Lee JY, Shimizu H, Hagio M, Fukiya S, Watanabe M, Tanaka Y, Joe GH, Iwaya H, Yoshitsugu R, Kikuchi K, Tsuji M, Baba N, Nose T, Tada K, Hanai T, Hori S, Takeuchi A, Furukawa Y, Shirouchi B, Sato M, Ooka T, Ogura Y, Hayashi T, Yokota A, Ishizuka S.
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Journal Title
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Volume: 1865
Issue: 12
Pages: 158811-158811
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Ingestion of difructose anhydride III reduces secondary bile acid concentration in rat large intestine.2019
Author(s)
Lee DG, Hori S, Kohmoto O, Kitta S, Yoshida R, Tanaka Y, Shimizu H, Takahashi K, Nagura T, Uchino H, Fukiya S, Yokota A, Ishizuka S.
Organizer
Kern Lipid Conference 2019
Related Report
Int'l Joint Research
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