Molecular mechanism of intracellular and in vivo function of an anorexic peptide, Nesfatin-1

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tokyo Medical and Dental University (2013); Gunma University (2011-2012)
• Principal Investigator: HASHIMOTO Koshi 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (30396642)
• Project Period (FY): 2011 – 2013
• Keywords: Nesfatin-1 / Nesfatin-1受容体 / 摂食抑制ペプチド / 細胞内シグナル伝達 / CREB / 膵β細胞 / 視床下部 / M30

Research Abstract

In the current study, we explored the intracellular signaling pathway of a hypothalamic anorexic hormone, Nesfatin-1 (NAP-1). Radioreceptor assays indicated that NAP-1 specific receptor should be located in the cell membrane fraction of mouse hypothalamus and of NB41A3 cells, which derived from mouse neuroblastoma. Through MAP kinase and L-type calcium channel, NAP-1 increased intracellular phosphorylation of cAMP response element binding protein (CREB). Moreover, it was revealed that in pancreatic beta cells, NAP-1 employed a distinct signaling pathway from that in central nervous system. We identified a candidate gene (GPCRn) for NAP-1 specific receptor and established GPCRn deficient mice (GPCRnKO).

Research Products

• [Journal Article] Discovery of nesfatin-1 and overview of biological actions and new developments (2013)
  • Author(s): Mori M, Yamada M, Okada S, Hashimoto K, Satoh T, Shimizu H, Yada T
  • Journal Title: Curr Pharm Des Volume: 19 Pages: 6921-6928
  • URL: http://www.eurekaselect.com/118383/article
  • Peer Reviewed
• [Journal Article] Nesfatin-1 Induces the Phosphorylation Levels of cAMP Response Element-Binding Protein for Intracellular Signaling in a Neural Cell Line (2012)
  • Author(s): Ishida E, Hashimoto K, Shimizu H, Okada S,Satoh T, Kato I, Yamada M, Mori M
  • Journal Title: PLoS One Volume: 7 Pages: e50918
  • DOI: 10.1371/journal.pone.0050918
  • Peer Reviewed
• [Journal Article] Secreted nucleobindin-2 inhibits 3T3-L1 adipocyte differentiation (2012)
  • Author(s): Tagaya Y, Osaki A, Miura A, Okada S, Ohshima K, Hashimoto K, Yamada M, Satoh T, Shimizu H, Mori M
  • Journal Title: Protein Pept Lett Volume: 19 Pages: 997-1004
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468916/pdf/PPL-19-997.pdf
  • Peer Reviewed
• [Presentation] Nesfatin-1 modulates the phosphorylation levels of cAMP response element binding protein for intracellular signaling in the neural and islet beta cell lines (2013)
  • Author(s): Koshi Hashimoto, Emi Ishida, Shigeki Takeda, Tetsurou Satoh, Shuichi Okada,Masanobu Yamada, Masatomo Mori
  • Organizer: 第36回内藤コンファレンス「分子からみたエネルギーバランスと摂食行動の制御」
  • Place of Presentation: シャトレーゼガトーキングダムサッポロ(北海道)
  • Year and Date: 20130910-13
• [Presentation] 摂食抑制ペプチドnesfatin-1の細胞内シグナル伝達機構の解析とその特異的受容体の探索 (2013)
  • Author(s): 橋本貢士,石田恵美,武田茂樹,登丸琢也,石井角保,小澤厚志,渋沢信行,佐藤哲郎,岡田秀一,清水弘行,山田正信,森昌朋
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 20130425-27
• [Presentation] 摂食抑制ペプチドnesfatin-1の細胞内シグナル伝達と受容体探索 (2012)
  • Author(s): 石田恵美,橋本貢士,三浦敦子,佐藤哲郎,岡田秀一,山田正信,清水弘行,森昌朋
  • Organizer: 第39回日本神経内分泌学会学術集会
  • Place of Presentation: 北九州国際会議場(福岡県)
  • Year and Date: 20120928-29
• [Presentation] 摂食抑制ペプチドnesfatin-1の細胞内シグナル伝達と受容体探索 (2012)
  • Author(s): 石田恵美,橋本貢士,三浦敦子,佐藤哲郎,岡田秀一,山田正信,清水弘行,森昌朋
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 20120517-19
• [Presentation] 摂食抑制因子nesfatin-1の受容体と細胞内シグナル伝達の探索 (2012)
  • Author(s): 石田恵美,橋本貢士,三浦敦子,佐藤哲郎,岡田秀一,山田正信,清水弘行,森昌朋
  • Organizer: 第85回日本内分泌学会学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 20120419-21
• [Presentation] 摂食抑制ペプチドnesfatin-1の細胞内シグナル伝達と受容体探索 (2011)
  • Author(s): 石田恵美、橋本貢士、三浦敦子、佐藤哲郎、岡田秀一、山田正信、清水弘行、森昌朋
  • Organizer: 第38回日本神経内分泌学会
  • Place of Presentation: 都道府県会館(東京都)
  • Year and Date: 2011-11-26
• [Presentation] 摂食抑制ペプチドnesfatin-1の受容体探索と細胞内シグナル伝達 (2011)
  • Author(s): 石田恵美、橋本貢士、佐藤哲郎、岡田秀一、山田正信、清水弘行、森昌朋
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌プリンスホテル(北海道)
  • Year and Date: 2011-05-19
• [Remarks]
  • URL: http://www.tmd.ac.jp/grad/cme/member/personal/hashimoto.html