Exercise improves obesity-related liver disease through a reduction of tissue damaging factor, TWEAK by the activation Nrf2.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H03255
• 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: Kuga Keisuke 筑波大学, 医学医療系, 教授 (60241816)
• Co-Investigator(Kenkyū-buntansha): 柳川 徹 筑波大学, 医学医療系, 教授 (10312852) ; 酒井 俊 筑波大学, 医学医療系, 講師 (30282362) ; 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) ; 正田 純一 筑波大学, 医学医療系, 教授 (90241827)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肥満 / 脂肪性肝疾患 / 運動療法 / 転写因子 / エンドトキシン / 炎症・酸化ストレス

Outline of Final Research Achievements

Not only nutritional support but also exercise for maintenance and/or increase of skeletal muscles are required in the clinical management of NAFLD. Exercise is effective to reduce liver fat contents irrespective of the exercise category. Moreover, high intense aerobic exercise is found to be effective for the improvement of oxidative liver pathological conditions. The molecular mechanism underlying the observations is an exertion of antioxidative stress action through exercise-induced activation of transcription factor Nrf2, in addition to the improvement of insulin resistance. Moreover, exercise-induced secretion of DHEA, etc. increased foreign body phagocytosis of Kupffer cells and in vivo clearance of intestinal bacteria-derived endotoxin, which in turn contributed to the improvement of inflammatory liver pathological conditions. Collectively, exercise is the most basic and continuous prevention and/or treatment of NAFLD.

Free Research Field

スポーツ医学

Academic Significance and Societal Importance of the Research Achievements

NAFLDはメタボリック症候群の肝における表現型である．NAFLDでは運動療法と食事療法が予防と治療の基本となるが，その予防や治療としての運動を含む身体活動（PA）に関するエビデンスは全般的に少ない．本研究では，肝脂肪蓄積や線維化を軽減するために必要なPAの強度，頻度，時間と種類は何かの質問に回答する成果を得た．また，マウスの動物実験より，走運動は転写因子Nrf2の活性化により生体の抗炎症酸化ストレス応答を増大させ，体重減少には依存せず，NAFLDの肝病態を改善するという新しい運動の分子メカニズムを解明した．