Exercise inhibits progression of obesity-related fatty liver disease through the regulation of activated innate immunity

• Project/Area Number: 24650436
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: TOGASHI Shinji 筑波大学, 医学医療系, 講師 (70361350)
• Co-Investigator(Kenkyū-buntansha): YANAGAWA Toru 筑波大学, 医学医療系, 准教授 (10312852) ; OHMORI Hajime 筑波大学, 体育系, 教授 (20223969) ; TANAKA Kiyoji 筑波大学, 体育系, 教授 (50163514) ; UTSUNOMIYA Hirotoshi 和歌山県立医科大学, 医学部, 准教授 (60264876) ; WARABI Eiji 筑波大学, 医学医療系, 講師 (70396612) ; SHODA Junichi 筑波大学, 医学医療系, 教授 (90241827)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肥満性肝疾患 / 脂肪性肝疾患 / 転写因子 / 肝代謝 / 骨格筋代謝 / 脂肪酸代謝 / 肥満 / 肥満関連肝疾患 / 自然免疫 / 酸化ストレス

Research Abstract

The molecular mechanism for usefullness of exercise on non-alcoholic fatty liver disease (NAFLD) has not been fully elucidated. The transcription factor Nrf2 regulates antioxidative stress system and activation of innate immunity. We tested the effects of exercise on NAFLD mice fed high fat and sucrose diet. The diet induced severe fat accumulation in the liver of wild-type and Nrf2KO mice. In wild-type mice, the exercise activated Nrf2 and then reduced the hepatic fat content. However, the Nrf2KO mice did not reduce the fat content. Taken together, it is suggested that exercise modifies body lipid metabolism and reduces hepatic fat content through the induction of Nrf2 activation.

Research Products

• [Journal Article] Peroxidoxin I plays a ptotective role against UVA irradiation through reduction of oxidative stress (2014)
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• [Journal Article] Expression of N-acetylglucosaminyl- transferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder (2014)
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  • Journal Title: J Gastroenterol Volume: 49 Pages: 702-714
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• [Journal Article] Effects of a low-volume aerobic-type interval exercise on VO2max and cardiac mass (2014)
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  • Journal Title: Medicine & Science in Sports & Exercise Volume: 46 Pages: 42-50
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• [Journal Article] Association of alcohol consumption with incident hypertension among middle-aged and older Japanese : The Ibaraki Prefectural Health Study (IPHS) (2014)
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  • Journal Title: Hypetension Volume: 63(1) Pages: 41-7
• [Journal Article] The relationship between reduction in abdominal fat in lifestyle management and obesity-related health risk factors (2014)
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  • Journal Title: Physical activity, moderate or vigorous exercise & NAFLD. Diabetes, Metab Syn & Obesity Volume: 未定 Issue: 5 Pages: 290-298
  • DOI: 10.1089/met.2013.0143
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• [Journal Article] Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet (2013)
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• [Journal Article] Exercise training decreases elevated serum ferritin and lipid peroxidation marker levels in middle-aged obese men with non- alcoholic fatty liver disease (2013)
  • Author(s): Oh S, Tanaka K, Warabi E, Shoda J
  • Journal Title: Medicine & Science in Sports & Exercise Volume: 45 Pages: 2214-22
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  • Author(s): Harada H, Warabi E, Matsuki T, Yanagawa T, Okada K, Uwayama J, Ikeda A, Nakaso K, Kirii K, Noguchi N, Bukawa H, Siow R, Mann G, Shoda J, Ishii T, Sakurai T
  • Journal Title: J Neuroscience Volume: 33 Pages: 14767-14777
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  • DOI: 10.4172/2165-7904.1000164
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• [Journal Article] Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis. (2013)
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• [Journal Article] Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder. (2013)
  • Author(s): Kenichiro Onuki
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  • DOI: 10.1007/s00535-013-0813-2
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• [Journal Article] Exercise training decreases elevated serum ferritin and lipid peroxidation marker levels in middle-aged obese men with non-alcoholic fatty liver disease (2013)
  • Author(s): Oh S, Tanaka K, Warabi E, Shoda J
  • Journal Title: Medicine & Science in Sports & Exercise Volume: 45 Pages: 2214-2222
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• [Journal Article] Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet (2013)
  • Author(s): 27. Okada K, Warabi E, Sugimoto H, Horie M, Gotoh N, Tokushige K, Hashimoto E, Utsunomiya H, Takahashi H, Ishii T, Yamamoto M, Shoda J
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• [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, Harada N, Taguchi K, Hashimoto E, Itoh K, Ishii T, Utsunomiya H, Yamamoto M, Shoda J
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• [Journal Article] Deletion of Nrf2leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M,Gotoh N, Tokushige K, Hashimoto E,Utsunomiya H, Takahashi H,Ishii T,Yamamoto M, Shoda J
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• [Presentation] 肥満者における肝病態の改善に向けた健康支援とその成果 (2013)
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  • Organizer: 第14回日本健康支援学会年次学術大会
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• [Presentation] 肥満者に対する加速度トレーニングの有用性に関する予備検討 (2013)
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  • Year and Date: 2013-03-08
• [Presentation] Nrf2遺伝子二重欠損マウスは過食によりNASHを自然発症する (2013)
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• [Presentation] 筋萎縮予防法ハイブリッド訓練の女性NAFLD患者に対する有用性の検討 (2013)
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  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics
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• [Presentation] 脂肪性肝炎を自然発症する過食肥満マウスの腸管病変と病態的意義, probioticsの効果 (2013)
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  • Organizer: 第99回日本消化器病学会
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• [Presentation] 胆道疾患 – 肥満・生活習慣病と胆道疾患 (2013)
  • Author(s): 正田純一
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  • Invited
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  • Organizer: 第68回日本体力医学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] p62:Nrf2遺伝子二重欠損マウスは過食によりNASHを自然発症する (2013)
  • Author(s): 蕨 栄治，秋山健太郎，正田純一
  • Organizer: 第17回日本肝臓学会大会
  • Place of Presentation: 神戸
• [Presentation] 肝病態における転写因子Nrf2の演じる生体防御機構 (2012)
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  • Organizer: 第7回臨床ストレス応答学会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-26
• [Presentation] 肥満と肝臓病, その予防と治療 (2012)
  • Author(s): 正田純一
  • Organizer: 第60回日本教育医学会記念大会
  • Place of Presentation: つくば市
  • Year and Date: 2012-08-26
• [Presentation] 非アルコール性脂肪性肝疾患(NAFLD)のProton magnetic resonance spectroscopy (1H-MRS)とControlled attenuation parameter (CAP)による異所性脂肪の非侵襲的診断と病態評価 (2012)
  • Author(s): 磯辺智範, 岡本嘉一, 正田純一
  • Organizer: 第39回日本肝臓学会東部会
  • Place of Presentation: 東京
• [Presentation] 運動療法は体重減少とは独立して肝病態と代謝異常を改善する (2012)
  • Author(s): 呉世昶, 田中喜代次, 正田純一
  • Organizer: 第16回日本肝臓学会大会
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• [Presentation] Nrf2/p62遺伝子二重欠損マウスは脂肪性肝炎を自然発症し肝腫瘍を発生する (2012)
  • Author(s): 岡田浩介, 蕨栄治, 正田純一
  • Organizer: 第16回日本肝臓学会大会
  • Place of Presentation: 神戸
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• [Presentation] 茨城県における肝がん疫学調査～中間報告より～ (2012)
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  • Place of Presentation: 金沢
• [Presentation] 非アルコール性脂肪性肝疾患(NAFLD)における骨格筋脂肪化が肝病態へ及ぼす影響 (2012)
  • Author(s): 岡本嘉一, 磯辺智範, 小野塚太郎, 志田隆史, 池田瑛, 南学, 正田純一
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] Nrf2/p62遺伝子二重欠損マウスは脂肪性肝炎を自然発症し肝腫瘍を発生する (2012)
  • Author(s): 岡田浩介, 蕨栄治, 徳重克年, 石井哲郎, 橋本悦子, 正田純一
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] 減量目的の運動療法が内臓型肥満者の肝および代謝病態に及ぼす影響について (2012)
  • Author(s): 呉世昶, 田中喜代次, 正田純一
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] 減量目的の運動療法が肥満者の肝病態に及ぼす影響について (2012)
  • Author(s): 呉世昶, 田中喜代次, 正田純一
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] 疾病モデルより解明された肝病態に対する転写因子Nrf2の演じる生体防御機構 (2012)
  • Author(s): 岡田浩介, 蕨栄治, 正田純一
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] 減量目的の運動療法が肥満者の肝病態に及ぼす影響について (2012)
  • Author(s): 小野塚太郎
  • Organizer: 第67回日本体力医学会総会
  • Place of Presentation: 岐阜
• [Presentation] Sarcopenic-obese, sarcopenic-lean and physically dependent status in older women
  • Author(s): NEMOTO M, YABUSHITA N, KIM M, SEINO S, JUNG S, OSUKA Y, OKUBO Y, RAFAEL F, TANAKA K
  • Organizer: The Annual Conference of the British Society of Gerontology
  • Place of Presentation: Oxford, UK
• [Book] Epidemiology and Pathogenesis of Hepatocellular Carcinoma. In : Hepatocellular Carcinoma (2014)
  • Author(s): Shoda J
  • Total Pages: 14
  • Publisher: NOVA Science Publishers(In press)
• [Book] 生活習慣と胆道癌-胆管癌集団発症への対策も含めてAnnual Review消化器2014 (2014)
  • Author(s): 正田純一
  • Publisher: 中外医学社
• [Book] 胆道の炎症内科学書第8版Vol.4肝・胆道・膵疾患 (2013)
  • Author(s): 正田純一
  • Total Pages: 3
  • Publisher: 中山書店
• [Book] 原発性硬化性胆管炎内科学書第8版Vol.4肝・胆道・膵疾患 (2013)
  • Author(s): 正田純一
  • Total Pages: 2
  • Publisher: 中山書店
• [Book] 健幸華齢のためのエクササイズ (2013)
  • Author(s): 田中喜代次(編集代表), 公益財団法人日本体育協会(監修)
  • Total Pages: 258
  • Publisher: サンライフ企画
• [Book] 専門医のための消化器病学 (2013)
  • Author(s): 正田純一
  • Total Pages: 3
  • Publisher: 医学書院
• [Book] 内科学書第8版 Vol.4 肝・胆道・膵疾患 (2013)
  • Author(s): 正田純一
  • Total Pages: 3
  • Publisher: 中山書店
• [Book] Gallbladder Cancer - Pathogenesis and Molecular Targeting Strategies for Therapeutic Options. In : Horizons in Cancer Research (2012)
  • Author(s): Shoda J, Kawamoto T, Yamamoto M
  • Publisher: NOVA Science Publishers
• [Book] Textbook of Traditional Japanese Medicine (2012)
  • Author(s): Junichi Shoda
  • Total Pages: 3
  • Publisher: Inchinkoto, Clinical efficacy and pharmacology
• [Patent(Industrial Property Rights)] 肝内胆管がんの検出, 判別方法 (2013)
  • Inventor(s): 正田純一
  • Industrial Property Rights Holder: 筑波大学
  • Acquisition Date: 2013-10-15