Effects of exercise-induced hormon "irisin" on NASH-related hepatoma

• Project/Area Number: 17K09444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: Takumi Kawaguchi 久留米大学, 医学部, 講師 (00320177)
• Co-Investigator(Kenkyū-buntansha): 橋田 竜騎 久留米大学, 医学部, 助教 (40754841) ; 谷口 英太郎 久留米大学, 医学部, 助教 (50341318)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マイオカイン / 運動 / 肝癌 / 非アルコール性脂肪性肝障害 / 筋肉量 / サルコペニア / 肝細胞癌 / デコリン / 非アルコール性脂肪肝炎 / 運動療法 / decorin / イリシン

Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) is a major etiology of hepatocellular carcinoma (HCC). Although muscle atrophy is associated with the development of HCC, it remains unclear an association between HCC and myokine, which is secreted from muscle fiber. The aim of this study is to examine effects of myokine on HCC in a mouse model of NASH-related HCC. In the mouse model of NASH-related HCC, serum levels of decorin, a myokine, was decreased compared to the control group. Moreover, decorin inhibited the proliferation of HCC in vitro study. These findings suggested that muscle atrophy may be associated with HCC proliferation through regulation of myokine.

Academic Significance and Societal Importance of the Research Achievements

本研究により、筋肉が分泌するホルモンであるdecorinが肝癌細胞の増殖に関わることが明らかとなった。Decorinにより肝癌細胞の増殖は抑制されることから、decorinは、近年増加傾向にあるNASH関連肝癌の新たな創薬ターゲットとなる可能性が示唆された。また、decorinは筋肉量とも相関を認めたことから、本研究により、社会的問題となっているサルコペニアの病態についても新たな知見が得られた。

Research Products

• [Journal Article] Clinical utility of the Liver Frailty Index for predicting muscle atrophy in chronic liver disease patients with hepatocellular carcinoma (2019)
  • Author(s): Hirota Keisuke、Kawaguchi Takumi、Koya Shunji、Nagamatsu Ayu、Tomita Manabu、Hashida Ryuki、Nakano Dan、Niizeki Takashi、Matsuse Hiroo、Shiba Naoto、Torimura Takuji
  • Journal Title: Hepatology Research Volume: 50 Issue: 3 Pages: 330-341
  • DOI: 10.1111/hepr.13453
  • Peer Reviewed
• [Journal Article] Slow walking speed overlapped with low handgrip strength in chronic liver disease patients with hepatocellular carcinoma (2019)
  • Author(s): Nagamatsu Ayu、Kawaguchi Takumi、Hirota Keisuke、Koya Shunji、Tomita Manabu、Hashida Ryuki、Kida Yohei、Narao Hayato、Manako Yuta、Tanaka Daisuke、Koga Noboru、Nakano Dan、Niizeki Takashi、Matsuse Hiroo、Torimura Takuji、Shiba Naoto
  • Journal Title: Hepatology Research Volume: 49 Issue: 12 Pages: 1427-1440
  • DOI: 10.1111/hepr.13405
  • Peer Reviewed
• [Journal Article] The association between sarcopenia and decorin, an exercise‐induced myokine, in patients with liver cirrhosis: a pilot study (2018)
  • Author(s): Bekki M, Hashida R, Kawaguchi T, Goshima N, Yoshiyama T, Otsuka T, Koya S, Hirota K, Matsuse H, Niizeki T, Torimura T, Shiba N
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle Rapid Communications Volume: 1
  • Peer Reviewed / Open Access
• [Journal Article] Profiles Associated with Sarcopenia in Hepatoma Patients Underwent Transcatheter Arterial Chemoembolization: A Data‐Mining Analysis (2018)
  • Author(s): Hirota K, Kawaguchi T, Hashida R, Koya S, Bekki M, Goshima N, Yoshiyama T, Otsuka T, Nozoe R, Nakano D, Shirono T, Shimose S, Iwamoto H, Niizeki T, Matsuse H, Koga H, Shiba N, Torimura T
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle ‐ Clinical Reports Volume: 3
  • Peer Reviewed / Open Access
• [Presentation] The Liver Frailty Index was Related to Hypoalbuminemia with Hyperglycemia, but not Muscle Mass, in Cirrhotic Patients with Hepatocellular Carcinoma: A Data-mining Analysis (2019)
  • Author(s): Kawaguchi T, Hirota K, Koya S, Hashida R, Nakano D, Shirono T, Shimose S, Iwamoto H, Niizeki T, Matsuse H, Shiba N and Torimura T
  • Organizer: The 70th Annual Meeting of the American Association for the Study of Liver Diseases
  • Int'l Joint Research
• [Presentation] がんリハビリテーションが進行肝癌患者のサルコペニアと予後におよぼす影響 (2019)
  • Author(s): 川口 巧、橋田竜騎、鳥村拓司
  • Organizer: 第23回日本肝臓学会大会
• [Presentation] In-hospital Exercise Prevented Sarcopenia in Hepatoma Patients with Chronic Liver Disease Who Underwent Transcatheter Arterial Chemoembolization (2018)
  • Author(s): Kawaguchi T, Koya S, Hashida R, Hirota K, Bekki M, Goshima N, Yoshiyama T, Otsuka T, Nozoe R, Nagamatsu A, Nakano D, Shirono T, Shimose S, Iwamoto H, Niizeki T, Matsuse H, Koga H, Shiba N, Torimura T
  • Organizer: The Liver Meeting 2018
  • Int'l Joint Research
• [Presentation] 運動療法が肝がん患者のサルコペニアにおよぼす影響 (2018)
  • Author(s): 川口 巧、中野 暖、橋田 竜騎、城野 智毅、下瀬 茂男、岩本 英希、相野 一、新関 敬、古賀 浩徳、志波 直人、鳥村 拓司
  • Organizer: 第104回 日本消化器病学会総会
• [Presentation] 肝疾患におけるサルコペニア 判定基準の比較と運動療法の効果 (2018)
  • Author(s): 川口 巧、中野 暖、鳥村 拓司
  • Organizer: 第54回 日本肝臓学会総会
• [Presentation] 有酸素運動とレジスタンス運動によるNAFLD改善効果の比較検討 (2017)
  • Author(s): 川口 巧、橋田 竜騎、鳥村 拓司
  • Organizer: 第103回 日本消化器病学会
• [Presentation] 運動療法が肝硬変患者のサルコペニアにおよぼす影響 (2017)
  • Author(s): 川口 巧、志波 直人、鳥村 拓司
  • Organizer: Japan Digestive Disease Week 2017
• [Presentation] Decorin, a Newly Identified Exercise-induced Myokine, was Associated with Sarcopenia in Patients with Liver Cirrhosis (2017)
  • Author(s): Ryuki Hashida, Takumi Kawaguchi, Shunji Koya, Keisuke Hirota, Goshima, Otsuka, Masafumi Bekki, Hiroo Matsuse, Jun Hayashi, Naoto Shiba, Takuji Torimura
  • Organizer: The Liver Meeting 2017
  • Int'l Joint Research