Elucidation of the role of Pin1 on the adipose differentiation

• Project/Area Number: 22659175
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: ASANO Tomoichiro 広島大学, 大学院・医歯薬学総合研究科, 教授 (70242063)
• Co-Investigator(Kenkyū-buntansha): NAKATSU Yusuke 広島大学, 大学院・医歯薬学総合研究科, 助教 (20452584)
• Co-Investigator(Renkei-kenkyūsha): SAKODA Hideyuki 東京大学, 大学病院, 助教 (50376464)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,230,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: メタボリックシンドローム / プロリン異性化酵素 / 脂肪細胞 / インスリン作用

Research Abstract

We reported that Pin1 binds to Crtc2 and suppresses CRE transcriptional and gluconeogenic activity in the liver. In addition, Pin1 associates with IRS-1, a major insulin receptor substrate, and enhances insulin-induced metabolic actions. The associations of Pin1 with IRS-1 and Crtc2 ultimately contribute to the incorporation of excess nutrients into tissues, based on a data series obtained using in vitro and in vivo over-expressions of Pin1, gene silencing, a specific inhibitor and Pin1 knock-out mice. In addition, it was shown that Pin1 is also indispensable for differentiation from pre-adipocytes into mature adipocytes.

Research Products

• [Journal Article] Prolyl isomerase Pin1 regulates mouse embryonic fibroblast differentiation into adipose cells (2012)
  • Author(s): Uchida., T., Furumai, K., Fukuda, T., Akiyama, H., Takezawa, M., Asano, T., Fujimori, F., and Uchida, C.
  • Volume: in press
  • Peer Reviewed
• [Journal Article] Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans (2012)
  • Author(s): Hasegawa, Y., Saito, T., Ogihara, T., Ishigaki, Y., Yamada, T., Imai, J., Uno, K., Gao, J., Kaneko, K., Shimosawa, T., Asano, T., Fujita, T., Oka, Y., and Katagiri, Y.
  • Volume: 125(9)
  • Pages: 1122-33
  • Peer Reviewed
• [Journal Article] Valsartan, independently of AT1 receptor or PPAR・ (2012)
  • Author(s): Iwasita, M., Sakoda, H., Kushiyama, A., Fujishiro, M., Ohno, H., Nakatsu, Y., Fukushima, T., Kumamoto, S., Tsuchiya, Y., Kikuchi, T., Kurihara, H., Akazawa, H., Komuro, I., Kamata, H., Nishimura, F. and Asano, T.
  • Journal Title: suppresses LPS-induced macrophage activation and improves insulin resistance in co-cultured adipocytes Am. J. Physiol. Cell Physiol. Volume: 302 Pages: 286-96
  • Peer Reviewed
• [Journal Article] Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development (2012)
  • Author(s): Kushiyama, A., Okubo, H., Zhang, J., Sakoda, H., Kikuchi, T., Fujishiro, M., Sato, H., Kushiyama, S., Iwashita, M., Nishimura, F., Fukushima, T., Nakatsu, Y., Kamata, H., Kurihara, H., Kikuchi, M., Kawazu, S., and Asano, T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 291-8
  • Peer Reviewed
• [Journal Article] LST8 level controls basal p70 S6 kinase and Akt phosphorylations, and mTORC1 and mTORC2 negatively regulate each other by competing for association with LST8 Obesity Res Clin Pract (2012)
  • Author(s): Kikuchi, T., Zhang, J., Sakoda, H., Koketsu, Y., Fujishiro, M., Kushiyama, A., Nakatsu, Y., Kamata, H., Inoki, K., Takahashi, S., Kurihara, H., Katagiri, H., Oka, Y., and Asano, T.
  • Volume: in press
  • Peer Reviewed
• [Journal Article] Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation (2012)
  • Author(s): Nakarai, H., Yamashita, A., Nagayasu, S., Iwashita, M., Kumamoto, S., Ohyama, H., Hata, M., Soga, Y., Kushiyama, A., Asano, T., Abiko, Y., and Nishimura, F.
  • Journal Title: Innate Immun Volume: 18 Pages: 164-70
  • Peer Reviewed
• [Journal Article] SGLT2阻害薬 (2012)
  • Author(s): 大野晴也、浅野知一郎
  • Journal Title: 月刊糖尿病 Volume: 12 Pages: 108-113
• [Journal Article] 骨格筋におけるインスリン抵抗性 (2012)
  • Author(s): 大野晴也、浅野知一郎
  • Journal Title: 骨格筋におけるインスリン抵抗性 Pages: 176-179
• [Journal Article] SGLT 2 阻害薬 カレントテラピー (2012)
  • Author(s): 大谷裕一郎、浅野知一郎
  • Journal Title: 治療薬 Volume: ７月号 Pages: 24-28
• [Journal Article] A deubiquitinating enzyme, USP7, is associated with insulin receptor substrates (IRSs) forming a negative feedback loop in insulin/insulin-like growth factor (IGF) signaling (2012)
  • Author(s): Yoshihara, H., Fukushima, T., Asano, T.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Prolyl isomerase Pin1 regulates mouse embryonic fibroblast differentiation into adipose cells (2012)
  • Author(s): Uchida., T., Furumai, K., Asano, T.
  • Journal Title: PLoS One Volume: (In press)
  • Peer Reviewed
• [Journal Article] Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of 3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages (2012)
  • Author(s): Kumamoto, S., kushiyama, A., Asano, T.
  • Journal Title: Obesity Res Clin Pract Volume: (In press)
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl Cis/ Trans Isomerase NIMA-interacting 1 Associates with Insulin Receptor Substrate-1 and Enhances Insulin Actions and Adipogenesis (2011)
  • Author(s): Nakatsu, Y., Sakoda, H., Kushiyama, A., Zhang, J., Ono, H., Fujishiro, M., Kikuchi, T., Fukushima, T., Yoneda, M., Ohno, H., Horike, N., Kanna, M., Tsuchiya, Y., Kamata, H., Nishimura, F., Isobe, T., Ogihara, T., Katagiri, H., Oka, Y., Takahashi, S., Kurihara, H., Uchida, T., and Asano, T.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 20812-22
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno, H., Nakatsu, Y., sakoda, H., Kushiyama, A., Ono, H., Fujishiro, M., Otani, Y., Okubo, H., Yoneda, M., Fukushima, T., Tsuchiya, Y., Kamata, H., Nishimura, F., Kurihara, H., Katagiri, H., Oka, Y., and Asano, T.
  • Journal Title: Am. J. Physiol. Cell Physiol Volume: 300 Pages: 47-54
  • Peer Reviewed
• [Journal Article] HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells (2011)
  • Author(s): Fukushima, T., Okajima, H., Yamanaka, D., Ariga, M., Nagata, S., Ito, A., Yoshida, M., Asano, T., Chida, K., Hakuno, F., and Takahashi, S.
  • Journal Title: Mol. Cell. Endocrinol Volume: 344 Pages: 81-9
  • Peer Reviewed
• [Journal Article] Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/ insulin-like growth factor-I receptor tyrosine kinases Biochem (2011)
  • Author(s): Fukushima, T., Arai, T., Ariga-Nedachi, M., Okajima, H., Ooi, Y., Iijima, Y., Sone, M., Cho, Y., Ando, Y., Kasahara, K., Ozon, A., Yoshihara, H., Chida, K., Okada, S., Kopchick, JJ., Asano, T., Hakuno, F., and Takahashi SI.
  • Journal Title: Biophys. Res. Commun Volume: 404 Pages: 767-73
  • Peer Reviewed
• [Journal Article] Calpain 6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1 J. (2011)
  • Author(s): Tonami, K., kurihara, Y., Arima, S., Nishiyama, K., Uchijima, Y., Asano, T., Sorimachi, H., and Kurihara, H.
  • Journal Title: Cell Sci Volume: 124 Pages: 1214-23
  • Peer Reviewed
• [Journal Article] mTORシグナルと糖脂質代謝異常 (2011)
  • Author(s): 迫田秀之、浅野知一郎
  • Journal Title: 実験医学 Volume: 29(6) Pages: 895-899
• [Journal Article] 糖輸送体 (2011)
  • Author(s): 大久保博史, 大野晴也, 浅野知一郎
  • Journal Title: G. I. Research Volume: 19(5) Pages: 412-417
• [Journal Article] HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells (2011)
  • Author(s): Fukushima, T., Okajima, H., Asano, T.
  • Journal Title: Mol.Cell.Endocrinol. Volume: 344 Pages: 81-9
  • Peer Reviewed
• [Journal Article] Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/insulin-like growth factor-I receptor tyrosine kinases (2011)
  • Author(s): Fukushima, T., Arai, T., Asano, T.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 404 Pages: 767-73
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl Cis/Trans Isomerase NIMA-interacting 1 Associates with Insulin Receptor Substrate-1 and Enhances Insulin Actions and Adipogenesis (2011)
  • Author(s): Nakatsu, Y., Sakoda, H., Asano T., et al.
  • Journal Title: J.Biol.Chem. Volume: 286 Pages: 20812-20822
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno, H., Nakatsu, Y., Asano T., et al.
  • Journal Title: Am.J.Physiol.Cell Physiol. Volume: 300
  • Peer Reviewed
• [Journal Article] HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells (2011)
  • Author(s): Fukushima, T., Okajima, H., Asano T., et al.
  • Journal Title: Mol.Cell.Endocrinol. Volume: 344 Pages: 81-89
  • Peer Reviewed
• [Journal Article] Calpain 6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1 (2011)
  • Author(s): Tonami, K., kurihara, Y., Asano T., et al.
  • Journal Title: J.Cell Sci. Volume: 124 Pages: 1214-1223
  • Peer Reviewed
• [Presentation] プロリン異性化酵素Par14のインスリンシグナルと糖・脂質代謝における役割 (2011)
  • Author(s): 張君、郭瑩、浅野知一郎
  • Organizer: 第23回分子糖尿病シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2011-11-26
• [Presentation] Roles of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 in non-alcoholic steatohepatitis (2011)
  • Author(s): 中津祐介、福嶋俊明、浅野知一郎
  • Organizer: 日本生化学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-24
• [Presentation] Nedd4 potentiates insulin signals through ubiquitination of IRS-2 in hepatocytes (2011)
  • Author(s): 福嶋俊明、浅野知一郎
  • Organizer: 日本生化学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-23
• [Presentation] 非アルコール性脂肪性肝炎(NASH)の発症におけるプロリン異性化酵素Pin1の役割 (2011)
  • Author(s): 迫田秀之、中津祐介、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-21
• [Presentation] レジスチン関連蛋白β(RELMβ)の非アルコール性脂肪性肝炎(NASH)の発症における役割 (2011)
  • Author(s): 大久保博士、中津祐介、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-21
• [Presentation] 転写共役因子CRTC3は高脂肪食によって発現誘導され、脂肪細胞分化と肝糖新生を促進する (2011)
  • Author(s): 浅野知一郎、中津祐介、迫田秀之
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] LST8肝過剰発現マウスの糖脂質代謝に与える影響の解析 (2011)
  • Author(s): 菊池貴子、迫田秀之、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] プロリン異性化酵素Pin1類似蛋白Par14/ 17の生理的役割解明 (2011)
  • Author(s): 大野晴也、迫田秀之、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] キサンチンオキシダーゼ経路のマクロファージ泡沫化と動脈硬化への関与 (2011)
  • Author(s): 櫛山暁史、迫田秀之、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] Trk(Trk-fused gene)はPTENに結合し、細胞内PIP3量を増加させることで、インスリン作用を促進させる (2011)
  • Author(s): 大谷裕一郎、中津祐介、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] 非アルコール性脂肪性肝炎(NASH)の発 (2011)
  • Author(s): 迫田秀之、中津祐介、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] ジスチン関連蛋白β(RELMβ)の非アルコール性脂肪性肝炎(NASH)の発症における役割 (2011)
  • Author(s): 大久保博士、中津祐介、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] モサプリドクエン酸塩の3T3-L1脂肪細胞におけるインスリン抵抗性改善作用の解明 (2011)
  • Author(s): 藤城緑、迫田秀之、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] プロリン異性化酵素Pin1類似蛋白Par14/17の生理的役割解明 (2011)
  • Author(s): 大野晴也、迫田秀之、浅野知一郎
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] Ubiquitination of insulin receptor substrate by Nedd4 potentiates insul in/IGF signals (2011)
  • Author(s): 福嶋俊明、浅野知一郎
  • Organizer: 日本生化学会中国四国支部会
  • Place of Presentation: 広島市
  • Year and Date: 2011-05-14
• [Presentation] Ubiquitination of insulin receptor substrate by Nedd4 potentiates insulin/IGF signals (2011)
  • Author(s): 福嶋俊明、浅野知一郎
  • Organizer: 日本生化学会中国四国支部会
  • Place of Presentation: 広島市
  • Year and Date: 2011-05-14
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/ikagaku/