Effect of medium-chain fatty acids on cardiac function

• Project/Area Number: 18K17726
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Nara Medical University
• Principal Investigator: Kawahara Isao 奈良県立医科大学, 医学部, 研究員 (80524975)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん性悪液質 / がん性心機能障害 / がん性心筋障害 / ミトコンドリア / 酸化ストレス / 中鎖脂肪酸 / グルコース / がん性心筋萎縮 / がん悪液質 / 心筋萎縮 / 心不全 / 心筋 / ミオグロビン / クレアチンキナーゼ

Outline of Final Research Achievements

The occurrence of cardiac dysfunction in cancer patients is the second leading cause of death after cancer death, but the details of myocardial damage derived from the cancer itself have not been clarified. Therefore, when an examination was conducted using in vitro and in vivo cachexia models, myocardial mitochondrial damage was induced by the cachexia. In the background, suppression of mitochondrial respiration and generation of oxidative stress were promoted. When a medium-chain fatty acid was used to promote mitochondrial oxidative phosphorylation, myocardial damage was suppressed. This finding is considered an important outcome expected to lead to dietary interventions that enable myocardial protection in cancer patients.

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん性心筋障害ががんそのものによりミトコンドリア呼吸の低下と酸化スレスの産生の増大を介して惹起されることが示された。これに対して、中鎖脂肪酸とグルコースの併用はがん性心筋障害を予防した。がん性心筋障害に対する予防や治療はほとんど知見がなかったが、本研究により食事介入によるがん性心筋障害の軽減が可能になると考えられる。より詳細な検討を今後加えることにより、早期の臨床応用を実現し、がん患者の社会的活動性や治療忍容性の改善をもたらし、予後改善につながることが期待される。

Research Products

• [Int'l Joint Research] 南通大学(中国)
• [Int'l Joint Research] Nantong University(中国)
• [Journal Article] Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model (2020)
  • Author(s): Nukaga Shota、Mori Takuya、Miyagawa Yoshihiro、Fujiwara‐Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Mori Shiori、Goto Kei、Kishi Shingo、Nakashima Chie、Ohmori Hitoshi、Kawahara Isao、Luo Yi、Kuniyasu Hiroki
  • Journal Title: Cancer Science Volume: 111 Issue: 12 Pages: 4605-4615
  • DOI: 10.1111/cas.14656
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of cancer-derived myocardial impairments using a mouse model (2020)
  • Author(s): Miyagawa Yoshihiro、Nukaga Shota、Mori Takuya、Fujiwara-Tani Rina、Fujii Kiyomu、Mori Shiori、Goto Kei、Kishi Shingo、Sasaki Takamitsu、Nakashima Chie、Ohmori Hitoshi、Kawahara Isao、Luo Yi、Kuniyasu Hiroki
  • Journal Title: Oncotarget Volume: 11 Issue: 41 Pages: 3712-3722
  • DOI: 10.18632/oncotarget.27759
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-stem cell property of pterostilbene in gastrointestinal cancer cells. (2020)
  • Author(s): Mori S, Kishi S, Honoki K, Fujiwara-Tani R, Moriguchi T, Sasaki T, Fujii K, Tsukamoto S, Fujii H, Kido A, Tanaka Y, Luo Y, Kuniyasu H.
  • Journal Title: Int J Mol Sci. Volume: 21 Issue: 24 Pages: 9347-9347
  • DOI: 10.3390/ijms21249347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Malic enzyme 1 is associated with tumor budding in oral squamous cell carcinomas. (2020)
  • Author(s): Nakashima C, Kirita T, Yamamoto K, Mori S, Luo Y, Sasaki T, Fujii K, Ohmori H, Kawahara I, Mori T, Goto K, Kishi S, Fujiwara-Tani R, Kuniyasu H
  • Journal Title: Int J Mol Sci Volume: 21 Issue: 19 Pages: 7149-7149
  • DOI: 10.3390/ijms21197149
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Proton Pump Inhibitors on Colorectal Cancer (2020)
  • Author(s): Sasaki Takamitsu、Mori Shiori、Kishi Shingo、Fujiwara-Tani Rina、Ohmori Hitoshi、Nishiguchi Yukiko、Hojo Yudai、Kawahara Isao、Nakashima Chie、Fujii Kiyomu、Luo Yi、Kuniyasu Hiroki
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 11 Pages: 3877-3877
  • DOI: 10.3390/ijms21113877
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting claudin‐4 enhances chemosensitivity in breast cancer (2020)
  • Author(s): Luo Yi、Kishi Shingo、Sasaki Takamitsu、Ohmori Hitoshi、Fujiwara‐Tani Rina、Mori Shiori、Goto Kei、Nishiguchi Yukiko、Mori Takuya、Kawahara Isao、Kondoh Masuo、Kuniyasu Hiroki
  • Journal Title: Cancer Science Volume: 111 Issue: 5 Pages: 1840-1850
  • DOI: 10.1111/cas.14361
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clostridium perfringens enterotoxin induced claudin-4 to activate YAP in oral squamous cell carcinomas. (2020)
  • Author(s): Nakashima C, Yamamoto K, Kishi S, Sasaki T, Ohmori H, Fujiwara-Tani R Mori S, Kawahara I, Nishiguchi Y, Mori T, Kondoh M, Luo Y, Kirita T, Kuniyasu H
  • Journal Title: Oncotarget Volume: 11 Issue: 4 Pages: 309-321
  • DOI: 10.18632/oncotarget.27424
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Magnetic Hyperthermia Using Self-Controlled Heating Elements Consisting of Fe-Al Milling Alloy Induces Cancer Cell Apoptosis while Preserving Skeletal Muscle (2019)
  • Author(s): Kawahara Isao、Goto Kei、Kodama Kenji、Luo Yi、Fujiwara-Tani Rina、Mori Takuya、Miyagawa Yoshihiro、Tanaka Hirokazu、Kodama Hiroyuki、Hosoito Nobuyoshi、Taniguchi Yukinori、Kuniyasu Hiroki
  • Journal Title: Pathobiology Volume: 86 Issue: 5-6 Pages: 254-262
  • DOI: 10.1159/000501524
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of Parameters for Cancer-Induced Sarcopenia in Patients Autopsied after Death from Colorectal Cancer (2019)
  • Author(s): Ohmori Hitoshi、Kawahara Isao、Mori Takuya、Nukaga Shota、Luo Yi、Kishi Shingo、Fujiwara-Tani Rina?、Mori Shiori、Goto Kei、Sasaki Takamitsu、Kuniyasu Hiroki
  • Journal Title: Pathobiology Volume: 86 Issue: 5-6 Pages: 306-314
  • DOI: 10.1159/000503037
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Targeting claudin‐4 enhances chemosensitivity of pancreatic ductal carcinomas (2019)
  • Author(s): Sasaki Takamitsu、Fujiwara‐Tani Rina、Kishi Shingo、Mori Shiori、Luo Yi、Ohmori Hitoshi、Kawahara Isao、Goto Kei、Nishiguchi Yukiko、Mori Takuya、Sho Masayuki、Kondo Masuo、Kuniyasu Hiroki
  • Journal Title: Cancer Medicine Volume: 8 Issue: 15 Pages: 6700-6708
  • DOI: 10.1002/cam4.2547
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Giving combined medium‐chain fatty acids and glucose protects against cancer‐associated skeletal muscle atrophy (2019)
  • Author(s): Mori Takuya、Ohmori Hitoshi、Luo Yi、Mori Shiori、Miyagawa Yoshihiro、Nukaga Shota、Goto Kei、Fujiwara‐Tani Rina、Kishi Shingo、Sasaki Takamitsu、Fujii Kiyomu、Kawahara Isao、Kuniyasu Hiroki
  • Journal Title: Cancer Science Volume: 110 Issue: 10 Pages: 3391-3399
  • DOI: 10.1111/cas.14170
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy (2019)
  • Author(s): Fujiwara-Tani Rina、Sasaki Takamitsu、Ohmori Hitoshi、Luo Yi、Goto Kei、Nishiguchi Yukiko、Mori Shiori、Nakashima Chie、Mori Takuya、Miyagawa Yoshihiro、Kawahara Isao、Fujii Kiyomu、Kishi Shingo、Tatsumoto Naokuni、Kuniyasu Hiroki
  • Journal Title: Pathobiology Volume: 86 Issue: 4 Pages: 182-189
  • DOI: 10.1159/000496027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy (2019)
  • Author(s): Fujiwara-Tani R, Sasaki T, Ohmori H, Luo Y, Goto K, Nishiguchi Y, Mori S, Nakashima C, Mori T, Miyagawa Y, Kawahara I, Fujii K, Kishi S, Tatsumoto N, Kuniyasu H
  • Journal Title: Pathobiology Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Magnetic hyperthermia using self-controlled heating elements consisting of Fe-Al milling alloy induces cancer cell apoptosis while preserving skeletal muscle. (2019)
  • Author(s): Kawahara I, Goto K, Kodama K, Luo Y, Fujiwara-Tani R, Mori T, Miyagawa Y, Tanaka H, Kodama H, Hirayama A, Hosoito N, Taniguchi Y, Miki Y, Kuniyasu H
  • Journal Title: Pathobiology Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Intermittent calorie restriction enhances epithelial- mesenchymal transition through alteration of energy metabolism in a mouse tumor model. (2018)
  • Author(s): Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H
  • Journal Title: Int J Oncol Volume: 52 Pages: 413-423
  • DOI: 10.3892/ijo.2017.4229
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pro-metastatic signaling of elaidic acid, a trans fatty acid, is associated with lipid rafts. (2018)
  • Author(s): Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Nakashima C, Sasaki T, Kuniyasu H
  • Journal Title: Oncol Lett Volume: 15 Pages: 4423-4426
  • DOI: 10.3892/ol.2018.7817
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of the long-chain fatty acid receptor GPR40 was associated with cancer progression in colorectal cancer. (2018)
  • Author(s): Nakashima C, Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H*
  • Journal Title: Oncol Lett Volume: 15 Pages: 8641-8646
  • DOI: 10.3892/ol.2018.8383
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intake of medium-chain fatty acids induces oxidative stress and to atrophy the myocardium (2018)
  • Author(s): Miyagawa Y, Mori T, Goto K, Fujiwara-Tani R, Kishi S, Sasaki T, Fujii K, Ohmori H, Kawahara I, Kuniyasu H
  • Journal Title: Lipids in Health and Disease Volume: 17 Issue: 1 Pages: 258-258
  • DOI: 10.1186/s12944-018-0908-0
  • Peer Reviewed / Open Access
• [Presentation] アミノ酸シスチン・テアニン摂取ががん悪液質マウスの骨格筋と腫瘍増殖に与える効果 (2020)
  • Author(s): 川原 勲、大森 斉、森 拓也、宮川良博、後藤 桂、額賀翔太、森 汐莉、岸 真五、谷 里奈、國安弘基
  • Organizer: 第109回日本病理学会総会
• [Presentation] 糖質と中鎖脂肪酸の併用経口投与は悪液質における癌関連骨格筋萎縮を抑制する (2020)
  • Author(s): 森 拓也、 大森 斉、川原 勲、宮川良博、後藤 桂、額賀翔太、森 汐莉、岸 真五、谷 里奈、國安弘基
  • Organizer: 第109回日本病理学会総会
• [Presentation] がん悪液質における心筋ミトコンドリア機能障害に対する中鎖脂肪酸の影響 (2020)
  • Author(s): 額賀翔太、大森 斉、森 拓也、宮川良博、後藤 桂、川原 勲、谷 里奈、岸 真吾、森 汐莉、國安弘基
  • Organizer: 第109回日本病理学会総会
• [Presentation] Effects of medium-chain fatty acids on cancer-derived myocardial atrophy (2020)
  • Author(s): Nukaga S, Mori T, Luo Y, Kawahara I, Miyagawa Y, Goto K, Fujiwara-Tani R, Kishi S, Mori S, Ohmori H, Kuniyasu H
  • Organizer: 79th Annual Meeting of Japanese Association for Cancer
• [Presentation] Effect of lauric acid intake on skeletal muscle atrophy caused by 5-FU treatment in CT26 colon cancer mouse model. (2020)
  • Author(s): Kawahara I, Mori T, Luo Y, Nukaga S, Miyagawa Y, Goto K, Ohmori H, Kuniyasu H
  • Organizer: 79th Annual Meeting of Japanese Association for Cancer
• [Presentation] がん悪液質は心筋細胞内の酸化ストレスの蓄積、オートファジーを亢進し、細胞の萎縮を誘導する (2019)
  • Author(s): 宮川良博，森 拓也，後藤 桂，川原 勲，藤井 澄、大森 斉、國安弘基
  • Organizer: 第108回日本病理学会総会
• [Presentation] がん悪液質における心筋ミトコンドリア機能障害に対する中鎖脂肪酸の効果 (2019)
  • Author(s): 額賀翔太、大森 斉、森 拓也、宮川良博、後藤 桂、川原 勲、國安弘基
  • Organizer: 第4回日本がんサポーティブケア学会学術集会
• [Presentation] Cancer cachexia induces myocardial atrophy by mitochondrial dysfunction producing oxidative stress (2019)
  • Author(s): Miyagawa Y, Ohmori H, Mori T, Nukaga S, Kawahara I, Goto K, Mori S, Kishi S, Kuniyasu H
  • Organizer: 78th Annual Meeting of Japanese Association for Cancer
• [Presentation] Effects of nutritional intervention on cancer-related skeletal muscle atrophy (2019)
  • Author(s): Kawahara I, Ohmori H, Mori T, Miyagawa Y, Nukaga S, Goto K, Mori S, Kishi S, Fujiwara-Tani R, Kuniyasu H
  • Organizer: 78th Annual Meeting of Japanese Association for Cancer
• [Presentation] Lauric acid, a medium-chain fatty acid protects myocardial mitochondria from dysfunction in cancer cachexia (2019)
  • Author(s): Nukaga S, Ohmori H, Mori T, Miyagawa Y, Goto K, Kawahara I, Fujiwara-Tani R, Kishi S, Mori S, Kuniyasu H
  • Organizer: 78th Annual Meeting of Japanese Association for Cancer
• [Presentation] 長鎖脂肪酸のがん間質細胞を介したがん幹細胞性の誘導 (2018)
  • Author(s): 川原 勲，宮川良博，森 拓也，後藤 桂，羅 奕、西口由希子、國安弘基
  • Organizer: 第107回日本病理学会総会、札幌市、2018.6.21-23
• [Presentation] Magnetic hyperthermia induces apoptosis in cancer cells and suppresses autop (2018)
  • Author(s): Kawahara I, Kuniyasu H, Miyagawa Y, Mori T, Goto K
  • Organizer: 77th Annual Meeting of Japanese Association for Cancer, Osaka, 2018.9.28-30
• [Remarks] 奈良県立医科大学分子病理学HP
  • URL: http://www.naramed-u.ac.jp/~molepath/