Whether methylated-(3")-epigallocatechin gallate is useful for the therapy of NASH(nonalcoholic steatohepatitis)?

• Project/Area Number: 21590864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: UENO Takato 久留米大学, 先端癌治療研究センター, 教授 (70176618)
• Co-Investigator(Renkei-kenkyūsha): NAKAYAMA Hitomi 久留米大学, 医学部, 講師 (20368955) ; HASHIMOTO Osamu 久留米大学, 医学部, 助教 (50289427)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 非アルコール性脂肪性肝炎(NASH) / 治療 / メチル化カテキン / 酸化ストレス / 炎症 / インスリン抵抗性 / メチオニン/コリン欠乏食 / サイトカイン / KKA^yマウス / メチオニン / コリン欠乏食

Research Abstract

After methylated-(3")-epigallocatechin gallate(MethylEGCG) was treated in the nonalcoholic steatohepatitis(NASH) model mice fed a methionine-choline-deficient diet(MCDD), infiltration of inflammatory cells, ballooning hepatocytes, Mallory-Denk body and pericellular fibrosis in the liver tissues improved. In addition, 8-hydro-2'-deoxyguanosine(8OhdG)-immunoreactive products in the hepatocytes were decreased, and the oxidative stress was suppressed. The protein expression of TNFR, pAkt and pNFκB was clearly decreased, and that of pIRS-1 was increased. From these results, MethylEGCG improved the liver injuries in the NASH model mice.

Research Products

• [Journal Article] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography (2012)
  • Author(s): Hotta K, et al(36人中25番目)
  • Journal Title: J Hum Genet Volume: 56 Pages: 716-719
  • Peer Reviewed
• [Journal Article] CD14 expression and Kupffer cell dysfunction in non-alcoholic steatohepatitis : Superparamagnetic iron oxide-magnetic resonance image and pathologic correlation (2012)
  • Author(s): Tonan T, Fujimoto K, Qayyum A, Morita Y, Nakashima O, Ono N, Kawahara A, Kage M, Hayabuchi N, Ueno T
  • Journal Title: J Gastroenterol Hepatol Volume: 27 Pages: 789-796
  • Peer Reviewed
• [Journal Article] Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women (2012)
  • Author(s): Hotta K, et al(35人中24番目)
  • Journal Title: J Hum Genet Volume: 57 Pages: 46-51
  • Peer Reviewed
• [Journal Article] Adiponectin suppresses endoplasmic reticulum stress in nonalcoholic steatohepatitis (2011)
  • Author(s): Ueno T, et al
  • Journal Title: Exp Ther Med Volume: 2 Pages: 1035-1040
  • Peer Reviewed
• [Journal Article] Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area (2011)
  • Author(s): Hotta K, et al(33人中22番目)
  • Journal Title: J Hum Genet Volume: 56 Pages: 716-719
  • Peer Reviewed
• [Journal Article] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population (2011)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 56 Issue: 9 Pages: 716-719
  • DOI: 10.1038/jhg.2011.74
  • Peer Reviewed
• [Journal Article] Human primary cultured hepatic stellate cells can be cryopreserved (2010)
  • Author(s): Nakamura A, Ueno T, et al
  • Journal Title: Med Mol Morphol Volume: 43 Pages: 107-115
  • NAID: 10026443533
  • Peer Reviewed
• [Journal Article] NAFLDに対する食事・運動療法 (2010)
  • Author(s): 上野隆登
  • Journal Title: 肝胆膵 Volume: 60 Pages: 999-1005
• [Journal Article] Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. (2010)
  • Author(s): Hotta K
  • Journal Title: BMC Medical Genetics Volume: 11
  • Peer Reviewed
• [Journal Article] Human primary cultured hepatic stellate cells can be cryopreserved. (2010)
  • Author(s): Nakamura A
  • Journal Title: Med Mol Morphol Volume: 43 Pages: 107-115
  • Peer Reviewed
• [Journal Article] Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue (2009)
  • Author(s): Ueno T, Torimura T, Nakamura T, Sivakumar R, Nakayama H, Otabe S, Yuan X, Yamada K, Hashimoto O, Inoue K, Koga H, Sata M
  • Journal Title: Int J Mol Med Volume: 24 Pages: 12-22
  • Peer Reviewed
• [Journal Article] Effects of adiponectin transgenic expression in liver of nonalcoholic steatohepatitis model mice (2009)
  • Author(s): Nakayama H, Otabe S, Yuan X, Ueno T, Hirota N, Fukutani T, Wada N, Hashinaga T, Yamada K
  • Journal Title: Clin & Exp Volume: 58 Pages: 901-908
  • Peer Reviewed
• [Journal Article] Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population (2009)
  • Author(s): Hotta K, et al(31人中20番目)
  • Journal Title: Am J Pathol Volume: 176 Pages: 168-176
  • Peer Reviewed
• [Journal Article] Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue (2009)
  • Author(s): Ueno T, Torimura T, Nakamura T, Sivakumar R, Nakayama H, Otabe S, Yuan X, Yamada K, Hashimoto O, Inoue K, Koga H, Sata M
  • Journal Title: International Journal of Molecular Medicine 24 Pages: 12-22
  • Peer Reviewed
• [Journal Article] Effects of adiponectin transgenic expression in liver of nonalcoholic steatohepatitis model mice (2009)
  • Author(s): Nakayama H, Otabe S, Yuan X, Ueno T, Hirota N, Fukutani T, Wada N, Hashinaga T, Yamada K
  • Journal Title: Metabolism : Clinical and Experimental 58 Pages: 901-908
  • Peer Reviewed
• [Journal Article] Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. 176:, 2010 (2009)
  • Author(s): Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Kamatani N, Nakamura Y
  • Journal Title: American Journal of Pathology 176 Pages: 168-176
  • Peer Reviewed
• [Journal Article] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population
  • Author(s): Hotta K, et al(30人中20番目)
  • Journal Title: J Hum Genet Volume: 56 Pages: 647-651
  • Peer Reviewed
• [Journal Article] 非アルコール性脂肪性肝疾患(NAFLD)患者のリハビリテーション
  • Author(s): 上野隆登
  • Journal Title: 臨床リハ Volume: 20 Pages: 328-333
• [Presentation] NASHにおけるKupffer細胞機能評価: SPIO-MRIと病理学的所見との相関 (2012)
  • Author(s): 東南辰幸
  • Organizer: 第18回肝血流動態イメージ研究会
  • Place of Presentation: 神戸
  • Year and Date: 2012-01-28
• [Presentation] NASHにおけるKupffer細胞機能評価:SPIO-MRIと病理学的所見との相関 (2012)
  • Author(s): 東南辰幸
  • Organizer: 第18回肝血流動態イメージ研究会
  • Place of Presentation: 神戸
  • Year and Date: 2012-01-28
• [Presentation] Therapeutic effects of metals and branched-chain amino acids in nonalcoholic steatohepatitis (2011)
  • Author(s): Ueno T
  • Organizer: The 62nd Annual Meeting of the American Association for the Study of Liver Diseases(AASLD)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-07
• [Presentation] Therapeutic effects of metals and branched-chain amino acids in nonalcoholic steatohepatitis (2011)
  • Author(s): Takato Ueno
  • Organizer: The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-07
• [Presentation] 非アルコール性脂肪性肝炎(NASH)に対する抗酸化微量栄養素の効果 (2011)
  • Author(s): 上野隆登
  • Organizer: 19th JDDW
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-21
• [Presentation] What microscopy can tell us about liver diseases (2011)
  • Author(s): Ueno T
  • Organizer: The 11th Interamerican Congress on Microscopy(CIASEM 2011)
  • Place of Presentation: Merida, Yucatan, Mexico
  • Year and Date: 2011-09-29
• [Presentation] What microscopy can tell us about liver diseases? (2011)
  • Author(s): Takato Ueno
  • Organizer: The 11th Interamerican Congress on Microscopy (CIASEM 2011)
  • Place of Presentation: Merida Yucatan, Mexico
  • Year and Date: 2011-09-29
• [Presentation] アディポネクチンは肝でのER stressを軽減しNASHの進展を抑制する (2011)
  • Author(s): 上野隆登
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-02
• [Presentation] Cytokine regulation in NASH (2010)
  • Author(s): Ueno T
  • Organizer: The 9th Single Topic Conference(JSH)"NASH 2010"
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2010-11-18
• [Presentation] Cytokine regulation in NASH. (2010)
  • Author(s): Ueno T
  • Organizer: The 9th Single Topic Conference (JSH) "NASH 2010"
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2010-11-18
• [Presentation] Adiponectin suppresses endoplasmic reticulum(ER) stress in nonalcoholic steatohepatitis(NASH) (2010)
  • Author(s): Ueno T
  • Organizer: The 61st Annual Meeting of the American Association for the Study of Liver Diseases(AASLD)
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-11-01
• [Presentation] Adiponectin suppresses endoplasmic reticulum (ER) stress in nonalcoholic steatohepatitis (NASH). (2010)
  • Author(s): Ueno T
  • Organizer: The 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-11-01
• [Presentation] Green tea catechin improves steatohepatitis in transgenic mice overexpressing nSREBP-1c in adipose tissue (2010)
  • Author(s): Ueno T
  • Organizer: 15th International Symposium on Cells of the Hepatic Sinusoid
  • Place of Presentation: Pasadena, USA
  • Year and Date: 2010-08-29
• [Presentation] Green tea catechin improves steatohepatitis in transgenic mice overexpressing nSREBP-1c in adipose tissue. (2010)
  • Author(s): Ueno T
  • Organizer: 15th International Symposium on Cells of the Hepatic Sinusoid
  • Place of Presentation: Pasadena, USA
  • Year and Date: 2010-08-29
• [Presentation] 非アルコール性脂肪性肝炎(NASH)におけるアディポネクチンの肝内での直接的関与に関する検討. (2010)
  • Author(s): 上野隆登
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形市
  • Year and Date: 2010-05-27
• [Presentation] Adiponectin expressed in liver directly improves nonalcoholic steatohepatitis(NASH) by way of anti-inflammation and anti-oxidative stress (2010)
  • Author(s): Nakayama H
  • Organizer: The 45th Annual Meeting of the European Association for the Study of the Liver(EASL)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-04-16
• [Presentation] Adiponectin expressed in liver directly improves nonalcoholic steatohepatitis (NASH) by way of anti-inflammation and anti-oxidative stress. (2010)
  • Author(s): Nakayama H
  • Organizer: The 45th Annual Meeting of the European Association for the Study of the Liver (EASL)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-04-16
• [Presentation] 緑茶エピガロカテキンガレートはNASH(非アルコール性脂肪性肝炎)肝のKupffer細胞を減少させ、抗炎症,抗酸化,インスリン感受性を誘導する (2009)
  • Author(s): 上野隆登
  • Organizer: 第38回日本肝臓学会西部会
  • Place of Presentation: 米子
  • Year and Date: 2009-12-04
• [Presentation] 緑茶エピガロカテキンガレートはNASH(非アルコール性脂肪性肝炎)肝の Kupffer 細胞を減少させ、抗炎症, 抗酸化, インスリン感受性を誘導する (2009)
  • Author(s): 上野隆登、鳥村拓司、佐田通夫
  • Organizer: 第38回日本肝臓学会西部会
  • Place of Presentation: 米子
  • Year and Date: 2009-12-04
• [Presentation] Molecular targeted therapy using natural food, Benifuki Tea methylEGCG(Metylated-(3)-epigallocatechin gallate) in hepatoma (2009)
  • Author(s): Hashimoto O
  • Organizer: 3rd International Kobe Liver Symposium on HCC with a JSH-ILCA Joint Scientific Session
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2009-06-07
• [Presentation] Molecular targeted therapy using natural food, Benifuki Tea methylegcg(Metylated-(3")-epigallocatechin gallate)in hepatoma -in vitro and in vivo approach- (2009)
  • Author(s): 橋本修, 鳥村拓司, 中村徹, 岩本英希, 上野隆登, 佐田通夫
  • Organizer: 3rd International Kobe Liver Symposium on HCC with a JSH-ILCA Joint Scientific Session
  • Place of Presentation: Kobe
  • Year and Date: 2009-06-07
• [Presentation] 緑茶カテキンはNASH(非アルコール性脂肪性肝炎)を改善する-nSREBP1-cトランスジェニックNASHモデルマウスによる検討- (2009)
  • Author(s): 上野隆登
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 緑茶カテキンはNASH(非アルコール性脂肪性肝炎)を改善する-nSREBP1cトランスジェニックNASHモデルマウスによる検討- (2009)
  • Author(s): 上野隆登、中村徹、中山ひとみ、小田辺修一、山田研太郎、森田恭代、橋本修、岩本英希、鳥村拓司、佐田通夫
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] NAFLDの発症病態に基づく治療戦略-nSREBP1cトランスジェニックマウスを用いた検討 (2009)
  • Author(s): 上野隆登
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-07
• [Book] 病気の分子形態学 (2011)
  • Author(s): 上野隆登
  • Total Pages: 370
  • Publisher: 学際企画
• [Book] アルコールと医学生物学 (2011)
  • Author(s): 花田慎一郎
  • Total Pages: 140
  • Publisher: 東洋書店
• [Book] 酸化ストレスと肝疾患 (2010)
  • Author(s): 中山ひとみ, 上野隆登, 他
  • Total Pages: 130
  • Publisher: 株式会社メディカルトリビューン
• [Book] 酸化ストレスと肝疾患 第6巻 (2010)
  • Author(s): 中山ひとみ
  • Total Pages: 130
  • Publisher: 株式会社メディカルトリビューン
• [Book] 酸化ストレスと肝疾患 (2009)
  • Author(s): 森田恭代, 上野隆登, 他
  • Total Pages: 147
  • Publisher: メデイカルトリビューン
• [Book] 酸化ストレスと肝疾患 第5巻 (2009)
  • Author(s): 森田恭代、上野隆登、田口順、石井邦英、安倍弘彦、黒松亮子、鳥村拓司、加藤絵美子、野田哲弘、立石行生、長田英輔、中島収、鹿毛政義、矢野博久、佐田通夫
  • Total Pages: 147
  • Publisher: メデイカルトリビューン
• [Book] アルコールと医学生物学
  • Author(s): 花田慎一郎, 上野隆登, 他
  • Total Pages: 140
  • Publisher: 東洋書店
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/sentanca/liver/content.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/sentanca/liver/content.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/sentanca/liver/content.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/sentanea/liver/content.html
• [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎の改善用組成物 (2010)
  • Inventor(s): 上野隆登,橋本修
  • Industrial Property Rights Holder: 久留米大学
  • Industrial Property Number: 2010-172131
  • Filing Date: 2010-07-30
• [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎の改善用組成物 (2010)
  • Inventor(s): 上野隆登 橋本修
  • Industrial Property Rights Holder: 久留米大学
  • Industrial Property Number: 2010-172131
  • Filing Date: 2010-07-30