The role of prolyl isomerase Pin1 in obesity

• Project/Area Number: 25461355
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: Nakatsu Yusuke 広島大学, 医歯薬保健学研究院(医), 助教 (20452584)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Pin1 / AMPK / 肥満 / Ｐｉｎ１ / ＡＭＰＫ / 膵β細胞 / Conditional Pin1 KO

Outline of Final Research Achievements

In this study, we investigated the role of prolyl ismoerase Pin1 in obesity . We identified AMPK gamma subunit as a Pin1 binding parter. Pin1 overexpression decreased AMPK phosphorylation by 2-deoxy-glucose, while Pin1 knockdown by siRNA enhanced. Pin1 canceled the protective effect of AMP on dephosphorylation, resulting in inducing the decrease of AMPK phosphorylation.
Lastly, we examined the phosphorylation levels of AMPK in mice muscle. We found Pin1 deficiency in muscle enhanced AMPK phosphorylation.
In summary, Pin1 regulates lipid metabolisn through decreasing AMPK phosphorylation.

Research Products

• [Journal Article] Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit. (2015)
  • Author(s): Nakatsu Y, Iwashita M, Sakoda H, Ono H, Nagata K, Matsunaga Y, Fukushima T, Fujishiro M, Kushiyama A, Kamata H, Takahashi S, Katagiri H, Honda H, Kiyonari H, Uchida T, Asano T.
  • Journal Title: J. Biol. Chem. Volume: ２９０ Pages: 24255-24266
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] プロリン異性化酵素Pin1を介した膵β細胞調節機構の解明 (2015)
  • Author(s): 中津 祐介、森 馨一、松永 泰花、迫田 秀之、櫛山 暁史、石原 寿光、浅野 知一郎
  • Organizer: 分子糖尿病学会
  • Place of Presentation: 東京（東京都）
  • Year and Date: 2015-12-05
• [Presentation] The role of prolyl isomerase Pin1 in pancreatic b cells (2015)
  • Author(s): 中津 祐介、森 馨一、松永 泰花、山本屋 武、山口 賢、石原 寿光、浅野 知一郎
  • Organizer: 分子生物学会
  • Place of Presentation: 神戸（兵庫県）
  • Year and Date: 2015-12-01
• [Presentation] The role of prolyl isomerase Pin1 in beta cell functions (2015)
  • Author(s): Yusuke Nakatsu, Keiichi Mori, Yasuka Matsunaga, Toshiaki Fukushima, Hideaki Kamata, Ken Yamaguchi, Hisamitsu Ishihara, Tomoichiro Asano
  • Organizer: American diabetes association
  • Place of Presentation: ボストン（アメリカ）
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] 膵β細胞のインスリン分泌におけるプロリン異性化酵素Pin1の役割 (2015)
  • Author(s): 中津祐介、森馨一、松永泰花、山本屋武、迫田秀之、藤城緑、櫛山暁史、石原寿光、浅野知一郎
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 下関（山口県）
  • Year and Date: 2015-05-21
• [Presentation] プロリン異性化酵素Pin1のβ細胞における役割の解明 (2014)
  • Author(s): 中津 祐介
  • Organizer: 分子糖尿病学会
  • Place of Presentation: 高知市文化プラザ
  • Year and Date: 2014-12-06
• [Presentation] 膵β細胞機能におけるプロリン異性化酵素Pin1の役割 (2014)
  • Author(s): 中津 祐介
  • Organizer: 分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] プロリン異性化酵素Pin1はAMPKgamma subunitに結合し、活性を抑制する (2014)
  • Author(s): 中津 祐介
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] プロリン異性化酵素Pin1はAMPKとPPARaを制御して脂質代謝に関与する (2013)
  • Author(s): 中津 祐介
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 熊本
• [Presentation] プロリン異性化酵素Pin1による新規AMPK機能制御機構の解明 (2013)
  • Author(s): 中津 祐介
  • Organizer: 分子生物学会
  • Place of Presentation: 神戸
• [Presentation] プロリン異性化酵素Pin1を介したAMPK機能制御機構の解明 (2013)
  • Author(s): 中津 祐介
  • Organizer: 分子糖尿病学シンポジウム
  • Place of Presentation: 大阪