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Research for usefulness of intestinal peptide, PYY_<3-36> for therapeutic agents of fatty liver and NASH

Research Project

Project/Area Number 16590650
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKurume University

Principal Investigator

UENO Takato  Kurume University, Research Center for Innovative Cancer Therapy, Professor, 先端癌治療研究センター, 教授 (70176618)

Co-Investigator(Kenkyū-buntansha) TORIYAMA Takuji  Kurume University, Second Department of Internal Medicine, Associate Professor, 医学部, 助教授 (60197986)
KOGA Hironori  Kurume University, Second Department of Internal Medicine, Assistant Professor, 医学部, 講師 (90268855)
HASHIMOTO Osamu  Kurume University, Second Department of Internal Medicine, Assistant, 医学部, 助手 (50289427)
川口 巧  久留米大学, 医学部, 助手 (00320177)
NAKAMURA Toru  Kurume University, Second Department of Internal Medicine, Assistant, 医学部, 助手 (30341332)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsFatty liver / NASH / PYY_<3-36> / Oxidative stress
Research Abstract

We examined the therapeutic effects of PYY_<3-36> on model animals showing obesity and fatty liver. Firstly, we studies using Zucker obesity model rats, and observed the effects of PYY_<3-36> in these rats. That is, 0-5μg/100g PYY per day was injected intraperitonialy for 30 days, and measured body weight point by point during observation term. In results, the increase of body weight of rats in the group treated with 5μg/100g PYY was significantly suppressed compared with that in the control group without treatment with PYY. However, nonalcoholic fatty liver diseases (NAFLD) containing nonalcoholic steatohepatitis (NASH) were not observed in liver tissues of these model rats. Next, we added the high calorie diet to the Zucker model rats for 1 month, and the characteristic findings of NASH such as intralobular inflammation, ballooning hepatocytes and Mallory's bodies were observed in the liver specimens. On the other hands, the histological findings of NASH were hardly observed in livers of the PYY-treated groups. However, the improvement of body weight was not recognized with PYY-treatment in this model rats, and we gave up a clinical trial, which treats with PYY in the patients with NAFLD and obesity.
Just at that moment, we reported that transgenic (Tg) mice which over express nSREBP-1c (nuclear sterol regulatory element-binding protein 1c) in fat tissues cause NASH. We examined the effects of green tea (-)-epigallocatechin-3-gallate (EGCG) in this nSREBP-1 Tg NASH model mice. That is, Water containing 0.05-0.1% EGCG was orally administrated for 3 months. In results, the increases of body weight and liver weight, and the progression of NASH were significantly suppressed with treatment of EGCG. Presently, we are studying whether the improvement of lipids, oxidative stress, insulin resistance and inflammation in the liver tissues are brought with EGCG treatment in the model mice.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (36 results)

All 2007 2006 2005 2004

All Journal Article (26 results) Book (4 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] Transgenic mice expressing unclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis2007

    • Author(s)
      Nakayama H, et al.
    • Journal Title

      Met Clin Exp 56

      Pages: 470-475

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transgenic mice expressing unclear sterol regulatory element-binding protein lc in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis2007

    • Author(s)
      Nakayama H, et al.
    • Journal Title

      Met Clin Exp 56

      Pages: 470-475

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Usefulness of serum hepatic fibrosis markers in the diagnosis of nonalcoholic steatohepatitis (NASH)2006

    • Author(s)
      Sasaki N, et al.
    • Journal Title

      Hepato-Gastroenterol 53

      Pages: 678-681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation2006

    • Author(s)
      Yoshida T, et al.
    • Journal Title

      Diabetologia 49

      Pages: 3094-3099

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] NASHの抗酸化療法2006

    • Author(s)
      上野隆登, 他
    • Journal Title

      肝胆膵 53

      Pages: 387-391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 肥満と肝疾患2006

    • Author(s)
      佐田通夫, 他
    • Journal Title

      日本内科学会雑誌 95

      Pages: 3-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma2006

    • Author(s)
      Shinichi Aishima, Yuji Basaki, Yoshinao Oda, Yousuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Fumihito Hosoi, Yuichiro Maruyama, Abbas Fotovati, Shinji Oie, Mayumi Ono, Takato Ueno, Michio Sata, Hirohisa Yano, Masamichi Kojiro, Michihiko Kuwano, Masuzumi Tsuneyoshi
    • Journal Title

      Cancer sci 97

      Pages: 1182-1190

    • NAID

      10019376997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Usefulness of serum hepatic fibrosis markers in the diagnosis of nonalcoholic steatohepatitis (NASH)2006

    • Author(s)
      Nozomi Sasaki, Takato Ueno, Yasuyo Morita, Eisuke Nagata, Michio Sata
    • Journal Title

      Hepatogastroenterol 53

      Pages: 678-681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 緑茶(カテキン)による発癌予防とその理論的背景2006

    • Author(s)
      上野隆登, 他
    • Journal Title

      肝胆膵 52

      Pages: 435-439

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The Wilson disease protein ATP7B resides in the late endo somes with Rab7 and the Niemann-Pick C1 protein2005

    • Author(s)
      Masaru Harada, et al.
    • Journal Title

      American Journal of Pathology 166・2

      Pages: 499-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of liver histology between patients with non-alcoholic steatohepatitis and patients with alcoholic steatohepatitis in Japan2005

    • Author(s)
      Morita, et al.
    • Journal Title

      Alcohol Clin Exp Res 29・12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes2005

    • Author(s)
      Morita Y, et al.
    • Journal Title

      Hepatogastroenterology 51・5

      Pages: 1338-1343

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NASHの糖尿病治療は?2005

    • Author(s)
      上野隆登
    • Journal Title

      肥満と糖尿病 4・6

      Pages: 1013-1016

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 類洞壁細胞の機能と生活習慣2005

    • Author(s)
      上野隆登, 他
    • Journal Title

      肝胆膵 51・11

      Pages: 659-666

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of liver histology between patients with non-alcoholic steatohepatitis and patients with alcoholic steatohepatitis in Japan2005

    • Author(s)
      Yasuyo Morita, Takato Ueno, Nozomi Sasaki, Kouichiro Kuhara, Shinichiro Yoshioka, Yukio Tateishi, Eisuke Nagata, Masayoshi Kage, Michio Sata
    • Journal Title

      Alcohol Clin Exp Res 29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes2005

    • Author(s)
      Yasuyo Morita, Takato Ueno, Nozomi Sasaki, Yukio Tateishi, Eisuke Nagata, Masayoshi Kage, Michio Sata
    • Journal Title

      Hepatogastroenterology 52

      Pages: 1338-1343

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pathogenesis and significance of restricted diet and exercise therapy in nonalcoholic steatohepatitis (NASH)2005

    • Author(s)
      Takato Ueno, Toru Nakamura, Nozomi Sasaki, Yasuyo Morita, Eisuke Nagata, Michio Sata
    • Journal Title

      NASH and Nutritional Therapy(Okita K ed)(Springer-Verlag)

      Pages: 84-91

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein2005

    • Author(s)
      Masaru Harada, et al.
    • Journal Title

      American Journal of Pathology 166・2

      Pages: 499-510

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 32004

    • Author(s)
      Takumi Kawaguchi, et al.
    • Journal Title

      American Journal of Pathology 165・5

      Pages: 1499-1508

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth factor-induced proliferation of human hepatic stellate cell line LI902004

    • Author(s)
      Ryuichiro Sakata, et al.
    • Journal Title

      Journal of Hepatology 40

      Pages: 52-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 32004

    • Author(s)
      Takumi Kawaguchi, Takafumi Yoshida, Masaru Harada, Takao Hisamoto, Yumiko Nagao, Tatsuya Ide, Eitaro Taniguchi, Hiroto Kumemura, Shinichiro Harada, Michiko Maeyama, Shinji Baba, Hironori Koga, Ryukichi Kumashiro, Takato Ueno, Hisanobu Ogata, Akihiko Yoshi
    • Journal Title

      Am J Pathol 165

      Pages: 1499-1508

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth factor-induced proliferation of human hepatic stellate cell line LI902004

    • Author(s)
      Ryuichiro Sakata, Takato Ueno, Toru Nakamura, Masaharu Sakamoto, Takuji Torimura, Michio Sata
    • Journal Title

      J Hepatol 40

      Pages: 52-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Innervation of the sinusoidal wall : regulation of the sinusoidal diameter2004

    • Author(s)
      Takato Ueno, et al.
    • Journal Title

      Anatomical Record 280A

      Pages: 868-873

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth factor-induced proliferation of human hepatic stellate cell2004

    • Author(s)
      Ryuichiro Sakata, et al.
    • Journal Title

      Journal of Hepatology 40

      Pages: 52-59

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma2004

    • Author(s)
      Takuji Torimura, et al.
    • Journal Title

      Journal of Hepatology 40

      Pages: 799-807

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Suppression of transforming growth factor-beta results in upregulation of transcription of regeneration factors after chronic liver injury2004

    • Author(s)
      Toru Nakamura, et al.
    • Journal Title

      Journal of Hepatology 41・6

      Pages: 974-982

    • Related Report
      2004 Annual Research Report
  • [Book] ~実地医家のための~早期糖尿病-糖尿病の早期治療と管理の実施へむけて-2006

    • Author(s)
      上野隆登
    • Publisher
      NASHを合併した糖尿病患者さんの治療法を教えて下さい。-NASHと糖尿病の関連性をみる-
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 〜実地医家のための〜早期糖尿病-糖尿病の早期治療と管理の実施へむけて-2006

    • Author(s)
      上野隆登
    • Publisher
      NASHを合併した糖尿病患者さんの治療法を教えて下さい。-NASHと糖尿病の関連性をみる-
    • Related Report
      2006 Annual Research Report
  • [Book] NASH and Nutritional Therapy2005

    • Author(s)
      Ueno T, et al.
    • Total Pages
      117
    • Publisher
      Springer-Verlag, Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Frontiers in Hepatology-NASH and Nutritional Therapy2004

    • Author(s)
      Takato Ueno, et al.
    • Total Pages
      117
    • Publisher
      Springer
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Patent(Industrial Property Rights)] メグリチニド類を含有する肝臓腺維化予防用医薬組成物2007

    • Inventor(s)
      上野隆登
    • Industrial Property Rights Holder
      学校法人 久留米大学, 味の素株式会社
    • Filing Date
      2007-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] メグリチニド類を含有する肝臓線維化予防用医薬組成物2007

    • Inventor(s)
      上野隆登
    • Industrial Property Rights Holder
      学校法人 久留米大学, 味の素株式会社
    • Filing Date
      2007-02-08
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 脂肪肝およびそれに起因する肝障害防止用高濃度カテキン含有機能性食品およびその用途2006

    • Inventor(s)
      上野隆登
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2006-002120
    • Filing Date
      2006-01-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ナテグリニドを含有する肝線維化抑制医薬組成物2006

    • Inventor(s)
      上野隆登
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2006-031269
    • Filing Date
      2006-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] III型プロコラーゲンのN末端のペプチド(P III P)の測定方法2004

    • Inventor(s)
      上野隆登
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2004-207476
    • Filing Date
      2004-07-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] III型プロコラーゲンのN末端のペプチド(PIIIPの測定方法2004

    • Inventor(s)
      上野 隆登
    • Industrial Property Rights Holder
      久留米大学
    • Industrial Property Number
      2004-207476
    • Filing Date
      2004-07-14
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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