Development of new prevention strategy of heart disease focusing on fatty acid metabolism and cardiac hormone FGF21
| Project/Area Number |
19K20107
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Ashikaga University (2021)
Gunma University (2019-2020) |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脂肪酸代謝 / 心筋梗塞 / 心不全 / FGF21 / ケトン体 |
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| Outline of Research at the Start |
生活習慣病の発症基盤である脂質代謝異常は、心筋梗塞や心不全などの心疾患発症に深く関与している。本研究では、エネルギー代謝を調節するホルモンとして同定された線維芽細胞増殖因子FGF21に着目し、脂肪酸代謝の変化による心臓での発現誘導のメカニズムを明らかにすることで、生活習慣病に伴う心疾患の病態におけるFGF21の役割を解明する。本研究により、内因性のFGF21を誘導させるような脂肪酸組成などの栄養状態の変化や薬剤、および食品の発見など、心疾患予防の新たなアプローチの可能性が広がると考えている。
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| Outline of Final Research Achievements |
We recently showed that fibroblast growth factor-21 (FGF21), anti-diabetic hormone predominantly produced by liver and adipose tissue, was also produced in the ischemic heart with increasing blood fatty acid concentration and contributed to induction of AMPK activity. Then, we found that both serum βOHB and FGF21 levels were significantly elevated in patients with heart failure compared with control group, and significant positive correlations of βOHB with FGF21. Given that oxidative stress is a key driver of heart disease and clear relevance to human pathologies, our findings suggest that increasing delivery of βOHB and FGF21 to the heart via AMPK/PPARα signaling pathway seems to be a promising therapeutic approach to heart disease.
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| Academic Significance and Societal Importance of the Research Achievements |
ケトン体は主に心臓や脳でエネルギー基質として利用されることは知られているが、ケトン体が心臓の脂肪酸代謝、エネルギー代謝および心疾患の病態形成におよぼす影響について、転写レベルでの研究はほとんど報告されていない。我々の結果から、FGF21とケトン体が心筋内の酸化ストレス応答因子の発現を制御するなど心筋保護的に作用することが明らかとなり、FGF21とケトン体が心疾患予防・治療の新たな標的因子となる可能性が示唆された。本研究成果により、内因性のFGF21発現を誘導するような脂質を基にした栄養療法や食品の発見、さらにはFGF21とケトン体を標的因子とした様々な臓器疾患の予防・治療への応用が期待される。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Urinary <scp>FABP1</scp> is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury2021
Author(s)
Kawakami Ryo, Matsui Miki, Konno Ayumu, Kaneko Ryosuke, Shrestha Suman, Sunaga Hiroaki, Hanaoka Hirofumi, Goto Sawako, Hosojima Michihiro, Kabasawa Hideyuki, Obokata Masaru, Koitabashi Norimichi, Matsui Hiroki, Sasaki Tsutomu, Saito Akihiko, Yanagita Motoko, Hirai Hirokazu, Kurabayashi Masahiko, Iso Tatsuya
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Journal Title
The Journal of Pathology
Volume: 255
Issue: 4
Pages: 362-373
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Ketone body as a signaling molecule to induce fibroblast growth factor 21:Implication for cardioprotective mechanism in heart failure.2020
Author(s)
Hiroaki Sunaga, Masaru Obokata, Ryo Kawakami, Hidemi Sorimachi, Tomonari Harada, Kuniko Yoshida, Toshimitsu Kato, Noriaki Takama, Norimichi Koitabashi, Tatsuya Iso, Hiroki Matsui, Tomoyuki Yokoyama, Masahiko Kurabayashi.
Organizer
第84回 日本循環器学会学術集会
Related Report
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[Presentation] Changes in Fatty Acid Composition by Elovl6 Ameliorates Pressure Overload-induced Cardiac Remodeling through Maintenance of Mitochondrial Integrity in Cardiac Myocyte.2019
Author(s)
Sayaka Tadaki, Hiroki Matsui, Hiroaki Sunaga, Yogi Umbarawan, Nozomi Furukawa, Tatsuya Iso, Norimichi Koitabashi, Takashi Matsuzaka, Hitoshi Shimano, Masahiko Kurabayashi, Tomoyuki Yokoyama.
Organizer
American Heart Association (AHA) Scientific Sessions 2019
Related Report
Int'l Joint Research
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