A energy shift from fatty acid to glucose is detrimental to pressure-overloaded heart
Project/Area Number |
26461123
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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 |
Research Field |
Cardiovascular medicine
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Research Institution | Gunma University |
Principal Investigator |
Iso Tatsuya 群馬大学, 大学院医学系研究科, 准教授 (10400756)
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Co-Investigator(Kenkyū-buntansha) |
倉林 正彦 群馬大学, 大学院医学系研究科, 教授 (00215047)
菱木 貴子 慶應義塾大学, 医学部(信濃町), 講師 (10338022)
小板橋 紀通 群馬大学, 医学部附属病院, 助教 (10420093)
山本 正道 京都大学, 医学研究科, 特任講師 (70423150)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 分子心臓病 / エネルギー代謝 / 脂肪酸 / グルコース / 心不全 / 構造リモデリング / 代謝リモデリング / 毛細血管 / 内皮細胞 |
Outline of Final Research Achievements |
Under increased workload, the heart shows structural (cardiac hypertrophy and fibrosis) and metabolic remodeling. Double knockout mice lacking FABP-4 and -5 and CD36 knockout mice exhibit reduced uptake of fatty acid with a robust increase in glucose uptake by metabolic compensation. When hearts were pressure-overloaded by trans-aortic constriction, cardiac contractile dysfunction was markedly exacerbated in both mice. Metabolic analysis revealed that pool size of the TCA cycle, or total energy supply, was significantly reduced despite a further increase in glucose uptake by TAC, leading to a reduction in ATP synthesis. In contrast, de novo synthesis of molecules for cardiac hypertrophy (i.e. amino acids, nucleic acids and fatty acids) was likely to be facilitated despite a reduction in total energy supply. Thus, the heart favors anabolic reactions rather than ATP synthesis during the development of cardiac hypertrophy even under conditions where total energy supply is limited.
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Early increase in serum fatty acid binding protein 4 in patients with acute myocardial infarction.2017
Author(s)
Obokata M, Iso T, Ohyama Y, Sunaga H, Kawaguchi T, Matsui H, Iizuka T, Fukuda N, Takamatsu H, Koitabashi N, Funada R, Takama N, Kasama S, Kaneko Y, Yokoyama T, Murakami M, Kurabayashi M.
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Journal Title
Eur Heart J Acute Cardiovascular Care
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart2015
Author(s)
Matsuhashi T, Hishiki T, Zhou H, Ono T, Kaneda R, Iso T, Yamaguchi A, Endo J, Katsumata Y, Atsushi A, Yamamoto T, Shirakawa K, Yan X, Shinmura K, Suematsu M, Fukuda K, Sano M
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Journal Title
J Mol Cell Cardiol
Volume: 82
Pages: 116-124
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Analysis of human cytomegalovirus replication in primary cultured human corneal endothelial cells.2015
Author(s)
Hosogai, M, Shima, N, Nakatani, Y, Inoue, T, Iso, T, Yokoo, H, Yorifuji, H, Akiyama, H, Kishi, S, Isomura, H.
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Journal Title
British Journal of Ophthalmology
Volume: 99
Issue: 11
Pages: 1583-1590
DOI
Related Report
Peer Reviewed
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[Journal Article] CD36 is indispensable for thermogenesis under conditions offasting and cold stress.2015
Author(s)
Putri M, Syamsunarno MR, Iso T, Yamaguchi A, Hanaoka H, Sunaga H, Koitabashi N, Matsui H, Yamazaki C, Kameo S, Tsushima Y, Yokoyama T, Koyama H, Abumrad NA, Kurabayashi M.
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Journal Title
Biochem Biophys Res Commun.
Volume: 457
Issue: 4
Pages: 520-525
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Vildagliptin Improves Ventricular Efficiency in Non-deabetic Pressure-overloaded Mouse Heart.2017
Author(s)
Furukawa N, Koitabashi N, Sunaga H, Obokata M, Yogi Umbarawan, Syamsunarno MRAA, Yamaguchi A, Matsui H, Iso T,Yokoyama T ,Kurabayashi M.
Organizer
第81回 日本循環器学会
Place of Presentation
金沢(石川県立音楽堂他)
Year and Date
2017-03-17
Related Report
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[Presentation] CD36 Plays a Crucial Role in Exercise Endurance During Prolonged Fasting in Mice.2016
Author(s)
Haruyama H, Iso T, Sunaga H, Umbarawan Y, Syamsunarno MRAA, Putri M, Matsui H, Yokoyama T, Kurabayashi M.
Organizer
The 89th annual meeting of American Heart Association
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, USA.
Year and Date
2016-11-12
Related Report
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[Presentation] A massive increase in serum levels of fatty acid binding protein 4 in patients with acute myocardial infarction complicated by out-of-hospital cardiac arrest due to ventricular fibrillation.2016
Author(s)
Sunaga H, Iso T, Obokata M, Ohyama Y, Koitabashi N, Funada R, Takama T, Matsui M, Yokoyama T, Murakami M, Kurabayashi M.
Organizer
The 89th annual meeting of American Heart Association
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, USA.
Year and Date
2016-11-12
Related Report
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[Presentation] A Preferential Change in Serum FABP4 Levels Compared with Free Fatty Acid after Onset of Acute Cardiovascular Events2016
Author(s)
Obokata M, Iso T, Sunaga H, Iizuka T, Ohyama Y, Ono Y, Fukuda N, Takamatsu H, Funada R, Takama N, Kasama S, Koitabashi N, Nakajima T, Kaneko Y, Kurabayashi M
Organizer
第80回日本循環器学会学術集会
Place of Presentation
仙台国際センター
Year and Date
2016-03-18
Related Report
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[Presentation] Early Increase in Serum Fatty Acid Binding Protein 4 Levels in Patients with Acute Myocardial Infarction: Lipolysis as a Novel Marker for Myocardial Ischemia.2014
Author(s)
Sunaga H, Ohyama Y, Obokata M, Iso T, Kawaguchi T, Koitabashi N, Funada R, Takama N, Syamsunarno MRAA, Matsui H, Yokoyama T, Kurabayashi M.
Organizer
The 87th annual meeting of American Heart Association
Place of Presentation
Chicago, USA
Year and Date
2014-11-14 – 2014-11-19
Related Report
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[Presentation] Glucose Uptake in the Heart of FABP4/5 double knockout mice is Promoted by Allosteric and Post-transcriptional Regulation of Glycolytic Pathways.2014
Author(s)
Tatsuya Iso, Kazuhisa Maeda, Hirofumi Hanaoka, Kosaku Goto, Mas Rizky A.A Syamsunarno, Takako Hishiki, Yoshiko Nagahata, Hiroki Matsui, Masashi Arai, Aiko Yamaguchi, Motoaki Sano, Makoto Suematsu, Keigo Endo, Gokhan S. Hotamisligil and Masahiko Kurabayashi.
Organizer
The 18th International Vascular Biology Meeting
Place of Presentation
Kyoto, Japan
Year and Date
2014-04-14 – 2014-04-17
Related Report
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