Exercise practice improves Kupffer cell function and reduces a risk of steatohepatitis and hepatic carcinogenesis.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H02174
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: SHODA JUNICHI 筑波大学, 医学医療系, 教授 (90241827)
• Co-Investigator(Kenkyū-buntansha): 柳川 徹 筑波大学, 医学医療系, 教授 (10312852) ; 呉 世昶 筑波大学, 医学医療系, 研究員 (10789639) ; 磯辺 智範 筑波大学, 医学医療系, 教授 (70383643) ; 蕨 栄治 筑波大学, 医学医療系, 講師 (70396612) ; 岡田 浩介 筑波大学, 附属病院, 病院講師 (80757526)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: NASH / LPS / Kupffer細胞 / 異物貪食能 / 運動実践 / 肥満モデル

Outline of Final Research Achievements

Intestinal bacteria-derived component, LPS, plays an important role in the onset and progression of non-alcoholic fatty liver disease (NAFLD). We found that in obese mice, p62KO, exercise practice increases the phagocytotic capacity of Kupffer cells. A long-term running exercise (with less than moderate intensity) for 3 months induced an improvement of inflammation and fibrosis in the liver histology of NAFLD, which was associated with the improved Kupffer cell function. This study revealed that exercise practice improved the NAFLD histology and attenuated the elevation of LPS concentration in the portal blood of p62KO. It shows for the first time that a continuous running exercise modifies in vivo LPS metabolism and inhibits NAFLD progression (fibrosis) in obese mice, p62KO.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

過食肥満マウスモデルにおいて，継続的走運動が門脈血中のLPSの代謝動態を変化させ，肝病態進展（線維化）を抑制することを初めて明らかにした．先行研究において，継続的走運動は腸内細菌叢を変化させること（Zhang C. et al., 2013, Kim D and Kang H., 2019）や，腸管透過性の亢進を抑制することが明らかになっている（Luo B. et al., 2014）．継続的走運動は，腸内細菌叢を変容させることや腸管透過性を低下させることで，門脈血中LPSの上昇を軽減したと考えられる．本結果は運動がNAFLDの病態改善に有用であることの分子メカニズムの一つであると考えられた．