Elucidation of the pathogenic mechanism of hyperuricemia in obesity and metabolic syndrome

• Project/Area Number: 23591340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Teikyo University
• Principal Investigator: HOSOYAMADA Makoto 帝京大学, 薬学部, 教授 (00291659)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Makiko 東京薬科大学, 薬学部, 助教 (80447557) ; ICHIDA Kimiyoshi 東京薬科大学, 薬学部, 教授 (80183169)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 高尿酸血症

Research Abstract

It was studied using a high-fat diet-treated mice and obesity model of ob/ob mice to elucidate mechanism for the development of hyperuricemia in obesity and metabolic syndrome. Among the expression of urate transporters URAT1, GLUT9, ABCG2 in the kidney of these mice, urate reabsorptive transporter URAT1 was significantly increased in the amount of protein expression while the amount of mRNA expression was invariant.
In order to see the changes in plasma uric acid by high-fat diet administration, we conducted the establishment of the method of breeding maintenance of uricase knockout mice which is lost uricase activity like humans, and we also established a strain of uricase-URAT1 double knockout mice.

Research Products

• [Journal Article] False in vitro and in vivo elevations of uric acid levels in mouse blood. (2014)
  • Author(s): Watanabe T, Tomioka NH, Watanabe S, Tsuchiya M, Hosoyamada M
  • Journal Title: Nucleosides, Nucleotides and Nucleic Acids Volume: 0
  • Peer Reviewed
• [Journal Article] Ependymal cells of the mouse brain express urate transporter 1 (URAT1) (2013)
  • Author(s): Tomioka NH, Nakamura M, Doshi M, Deguchi Y, Ichida K, Morisaki T, Hosoyamada M
  • Journal Title: Fluids Barriers CNS Volume: 10(1) Pages: 31-31
• [Journal Article] Common dys-functional variants in ABCG2 are a major cause of early-onset gout (2013)
  • Author(s): Matsuo H, Ichida K, Takada T, Nakayama A, Nakashima H, Nakamura T, Kawamura Y, Takada Y, Yamamoto K, Inoue H, Oikawa Y, Naito M, Hishida A, Wakai K, Okada C, Shimizu S, Sakiyama M, Chiba T, Ogata H, Niwa K, Hosoyamada M, Mori A, Hamajima N, Suzuki H, Kanai Y, Sakurai Y, Hosoya T, Shimizu T, Shinomiya N
  • Journal Title: Sci Rep Volume: 3 Pages: 2014-2014
• [Journal Article] Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic db/db mice (2013)
  • Author(s): Watanabe T, Tomioka NH, Doshi M, Watanabe S, Tsuchiya M, Hosoyamada M
  • Journal Title: Biol Pharm Bull Volume: 36(5) Pages: 741-747
  • NAID: 130003361408
• [Journal Article] Ependymal cells of the mouse brain express urate transporter 1 (URAT1) (2013)
  • Author(s): Tomioka NH, Nakamura M, Doshi M, et al
  • Journal Title: Fluids Barriers CNS Volume: 10 Issue: 1 Pages: 31-31
  • DOI: 10.1186/2045-8118-10-31
  • URL: https://localhost/en/publications/b7fc28c5-aeeb-449d-8cb7-555bce81ffa1
  • Peer Reviewed
• [Journal Article] Common dysfunctional variants in ABCG2 are a major cause of early-onset gout. (2013)
  • Author(s): Matsuo, H. Ichida, K. Takada, T. et al.
  • Journal Title: Scientific reports Volume: 3：2014 Issue: 1 Pages: 2014-2014
  • DOI: 10.1038/srep02014
  • Peer Reviewed
• [Journal Article] Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic db/db mice. (2013)
  • Author(s): Watanabe T, Tomioka NH, Doshi M, Watanabe S, Tsuchiya M, Hosoyamada M.
  • Journal Title: Biol Pharm Bull. Volume: 36(5) Pages: 741-747
  • NAID: 130003361408
  • Peer Reviewed
• [Journal Article] Decreased extra-renal urate excretion is a common cause of hyperuricemia (2012)
  • Author(s): Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, Yamanashi Y, Kasuga H, Nakashima H, Nakamura T, Takada Y, Kawamura Y, Inoue H, Okada C, Utsumi Y, Ikebuchi Y, Ito K, Nakamura M, Shinohara Y, Hosoyamada M, Sakurai Y, Shinomiya N, Hosoya T, Suzuki H
  • Journal Title: Nat Commun Volume: 3 Pages: 764-770
• [Journal Article] Decreased extra-renal urate excretion is a common cause of hyperuricemia (2012)
  • Author(s): Kimiyoshi Ichida, Hirotaka Matsuo, Tappei Takada, et al (Hiroshi Suzuki)
  • Journal Title: Nature Communication Volume: 3 Issue: 1 Pages: 1-7
  • DOI: 10.1038/ncomms1756
  • URL: https://localhost/en/publications/719645f5-4ec4-4f6b-a2a8-f58d7f666857
  • Peer Reviewed
• [Journal Article] The increased protein level of URAT1 was observed in obesity/metabolic syndrome model mice (2011)
  • Author(s): Doshi M, Takiue Y, Saito H, Hosoyamada M
  • Journal Title: Nucleosides Nucleotides Nucleic Acids Volume: 30(12) Pages: 1290-4
• [Journal Article] The increased protein level of URAT1 was observed in obesity/metabolic syndrome model mice. (2011)
  • Author(s): Doshi M, Takiue Y, Saito H, Hosoyamada M.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. Volume: 30(12): Pages: 1290-4
  • Peer Reviewed
• [Presentation] マウスにおける採血前および採血後偽高尿酸血症 (2014)
  • Author(s): 渡部多真紀,富岡直子,渡辺茂和,土屋雅勇,細山田真
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] Urate transporter 1 (URAT1)は脳室上衣細胞に発現する (2014)
  • Author(s): 富岡直子、中村真希子、出口芳春、市田公美、森崎隆幸、細山田真
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2014-03-21
• [Presentation] マウス脳内URAT1は脳室上衣細胞脳室側膜に局在する (2014)
  • Author(s): 富岡直子、中村真希子、市田公美、森崎隆幸、内田俊也、細山田真
  • Organizer: 第47回日本痛風核酸代謝学会
  • Place of Presentation: 神戸
  • Year and Date: 2014-02-21
• [Presentation] マウスの採血前および採血後偽高尿酸血症 (2013)
  • Author(s): 渡部多真紀,富岡(原)直子,道志勝,渡辺茂和,細山田真,土屋雅勇
  • Organizer: 第57回日本薬学会関東支部大会
  • Place of Presentation: 東京
  • Year and Date: 2013-10-26
• [Presentation] FALSE INCREASE OF URIC ACID LEVEL OF MOUSE BLOOD IN VITRO (2013)
  • Author(s): Hosoyamada-M, Watanabe-T, Tomioka-NH, Doshi-M, Watanabe-S, Tsuchiya-M
  • Organizer: 15th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2013-06-10
• [Presentation] 家族性若年性高尿酸血症性腎症1型モデルマウス腎臓では5'-レダクターゼ2発現が増加する (2013)
  • Author(s): 細山田真、富岡直子、道志勝
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-05-11
• [Presentation] ヘパリン加マウス血液のα受容体刺激による尿酸生成 (2013)
  • Author(s): 細山田真、渡部多真紀、富岡直子、道志勝、土屋雅勇
  • Organizer: 第86回日本薬理学会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-21
• [Presentation] マウス血清尿酸値のインビトロ上昇 (2013)
  • Author(s): 渡部多真紀、富岡直子、中村真希子、道志勝、金子希代子、内田俊也、藤森新、市田公美、土屋雅勇、細山田真
  • Organizer: 第46回日本痛風・核酸代謝学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-02-14
• [Presentation] マウス血清尿酸値のインビトロ上昇 (2013)
  • Author(s): 渡部 多真紀、富岡 直子、中村 真希子、道志 勝、金子 希代子、内田 俊也、藤森 新、市田 公美、土屋 雅勇、細山田 真
  • Organizer: 第46回 日本痛風・核酸代謝学会総会
  • Place of Presentation: 東京
• [Presentation] ヘパリン加マウス血液のα受容体刺激による尿酸生成 (2013)
  • Author(s): 細山田 真、渡部 多真紀、富岡 直子、道志 勝、土屋 雅勇
  • Organizer: 第86回 日本薬理学会
  • Place of Presentation: 福岡
• [Presentation] Fluoresceinを用いた尿酸トランスポーター機能評価法の開発 (2012)
  • Author(s): 中村真希子、荒川伸介、松尾広大、細山田真、安西尚彦、市田公美
  • Organizer: 第45回日本痛風・核酸代謝学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2012-02-17
• [Presentation] ウリカーゼノックアウトマウスにおけるアロプリノール投与の影響 (2012)
  • Author(s): 細山田真、金子希代子、内田俊也、藤森新
  • Organizer: 第45回日本痛風・核酸代謝学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2012-02-17
• [Presentation] 家族性若年性高尿酸血症性腎症1型モデルマウス腎臓では5’-レダクターゼ2発現が増加する
  • Author(s): 細山田 真、富岡 直子、道志 勝
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京
• [Presentation] マウスの採血前および採血後偽高尿酸血症
  • Author(s): 渡部多真紀，富岡（原）直子，道志 勝，渡辺茂和，細山田真，土屋雅勇
  • Organizer: 第57回日本薬学会関東支部大会
  • Place of Presentation: 東京
• [Presentation] マウス脳内URAT1は脳室上衣細胞脳室側膜に局在する
  • Author(s): 富岡 直子、中村 真希子、市田 公美、森崎 隆幸、内田 俊也、細山田 真
  • Organizer: 第47回日本痛風核酸代謝学会
  • Place of Presentation: 神戸
• [Presentation] Urate transporter 1 (URAT1) は脳室上衣細胞に発現する
  • Author(s): 富岡 直子、中村 真希子、出口 芳春、市田 公美、森崎 隆幸、細山田 真
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] マウスにおける採血前および採血後偽高尿酸血症
  • Author(s): 渡部 多真紀，富岡 直子，渡辺 茂和，土屋 雅勇，細山田 真
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] ウリカーゼノックアウトマウスにおけるアロプリノール投与の影響
  • Author(s): 細山田 真、金子 希代子、内田 俊也、藤森 新
  • Organizer: 第45回日本痛風・核酸代謝学会総会
  • Place of Presentation: 奈良