The effect of high-fat low-carbon diet on cardiac function and metabolism

• Project/Area Number: 26461124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Toko Haruhiro 東京大学, 医学部附属病院, 特任助教 (40436358)
• Research Collaborator: HARADA Mutsuo ; KO Toshiyuki ; MURAKAMI Haruka ; ISHIZUKA Masato
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 高脂肪低炭水化物食 / 心肥大 / 心不全 / 食事組成 / 食事療法

Outline of Final Research Achievements

In a failing heart, a workload of each cardiomyocyte is increased to recover cardiac function. Although the increase requires more energy, failing cardiac cells are reported not to product enough energy. High fat diet is reported to reactivate lipid metabolism and increase energy product. So, we examined whether high fat low carbon (HFLC) diet could preserve cardiac function in murine failing models via an increase of energy production.
Our results showed that HFLC did not increase energy production, but HFLC decreased cardiac hypertrophy in a pressure-overload model and preserved cardiac function in a dilated cardiomyocyte model. We are studying mechanisms of how HFLC keeps cardiac function under pathological conditions.

Research Products

• [Journal Article] Prostaglandin E2 Signaling as a Target of Anti-Cardiac Fibrosis in Heart Failure Treatment (2017)
  • Author(s): Harada M, Takeda N, Toko H.
  • Journal Title: International Heart Journal Volume: 58 Issue: 1 Pages: 3-4
  • DOI: 10.1536/ihj.16-614
  • NAID: 130005330498
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. (2017)
  • Author(s): Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I.
  • Journal Title: PLoS One. Volume: 12 Issue: 3 Pages: 0174099-0174099
  • DOI: 10.1371/journal.pone.0174099
  • Peer Reviewed / Open Access
• [Journal Article] Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes (2016)
  • Author(s): Takeda N, Yagi H, Hara H, Fujiwara T, Fujita D, Nawata K, Inuzuka R, Taniguchi Y, Harada M, Toko H, Akazawa H, Komuro I.
  • Journal Title: International Heart Journal Volume: 57 Issue: 3 Pages: 271-277
  • DOI: 10.1536/ihj.16-094
  • NAID: 130005153709
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Does Mechanical Stress Regulate the Angiogenic Profile of Endothelial Progenitor Cells? (2016)
  • Author(s): Harada M, Toko H.
  • Journal Title: International Heart Journal Volume: 57 Issue: 3 Pages: 268-270
  • DOI: 10.1536/ihj.16-168
  • NAID: 130005153710
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] S100A4 protects the myocardium against ischemic stress. (2016)
  • Author(s): Doroudgar S, Quijada P, Konstandin M, Ilves K, Broughton K, Khalafalla FG, Casillas A, Nguyen K, Gude N, Toko H, Ornelas L, Thuerauf DJ, Glembotski CC, Sussman MA, Volkers M.
  • Journal Title: J Mol Cell Cardiol. Volume: 100 Pages: 54-63
  • DOI: 10.1016/j.yjmcc.2016.10.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Notch activation enhances lineage commitment and protective signaling in cardiac progenitor cells. (2015)
  • Author(s): Gude N, Joyo E, Toko H, Quijada P, Villanueva M, Hariharan N, Sacchi V, Truffa S, Joyo A, Voelkers M, Alvarez R, Sussman MA.
  • Journal Title: Basic Res Cardiol Volume: 110 Issue: 3
  • DOI: 10.1007/s00395-015-0488-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling (2015)
  • Author(s): Kumagai H, Ikeda Y, Motozawa Y, Fujishiro M, Okamura T, Fujio K, Okazaki H, Nomura S, Takeda N, Harada M, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Yamamoto K, Komuro I, Yanagisawa M
  • Journal Title: PLoS One Volume: 10 Issue: 5 Pages: e0129394-e0129394
  • DOI: 10.1371/journal.pone.0129394
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monitoring beta-arrestin recruitment via beta-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors (2015)
  • Author(s): Ikeda Y*, Kumagai H*, Okazaki H, Fujishiro M, Motozawa Y, Nomura S, Takeda N, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Komuro I, Yanagisawa M (co-first author)
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0127445-e0127445
  • DOI: 10.1371/journal.pone.0127445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy. (2015)
  • Author(s): Wade F, Quijada P, Al-Haffar KM, Awad SM, Kunhi M, Toko H, Marashly Q, Belhaj K, Zahid I, Al-Mohanna F, Stanford SM, Alvarez R, Liu Y, Colak D, Jordan MC, Roos KP, Assiri A, Al-Habeeb W, Sussman M, Bottini N, Poizat C.
  • Journal Title: J Pathol Volume: 237 Issue: 4 Pages: 482-94
  • DOI: 10.1002/path.4594
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic dysfunction consistent with premature aging results from deletion of Pim kinases (2014)
  • Author(s): Din S, Konstandin MH, Johnson B, Emathinger J, Volkers M, Toko H, Collins B, Ormachea L, Samse K, Kubli DA, De La Torre A, Kraft AS, Gustafsson AB, Kelly DP, Sussman MA.
  • Journal Title: Circ Res Volume: 115 Issue: 3 Pages: 376-387
  • DOI: 10.1161/circresaha.115.304441
  • Peer Reviewed
• [Journal Article] Differential regulation of cellular senescence and differentiation by prolyl isomerase Pin1 in cardiac progenitor cells (2014)
  • Author(s): Toko H, Hariharan N, Konstandin MH, Ormachea L, McGregor M, Gude NA, Sundararaman B, Joyo E, Joyo AY, Collins B, Din S, Mohsin S, Uchida T, Sussman MA
  • Journal Title: J Biol Chem Volume: 289 Issue: 9 Pages: 5348-5356
  • DOI: 10.1074/jbc.m113.526442
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac progenitor cells engineered with βARKct have enhanced β-adrenergic tolerance (2014)
  • Author(s): Khan M, Mohsin S, Toko H, Alkatib M, Nguyen J, Truffa S, Gude N, Chuprun K, Tilley DG, Koch WJ, Sussman MA
  • Journal Title: Mol Ther Volume: 22 Issue: 1 Pages: 178-185
  • DOI: 10.1038/mt.2013.200
  • Peer Reviewed / Open Access
• [Presentation] 低炭水化物高脂肪食は拡張型心筋症の心機能低下を抑制する (2016)
  • Author(s): 東口治弘
  • Organizer: 日本心筋症研究会
  • Place of Presentation: まつもと市民芸術館（長野県松本市）