Finding the way to control ghrelin activity for the obesity cure

• Project/Area Number: 26461331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Wakayama Medical University (2015-2016); Kyoto University (2014)
• Principal Investigator: Hiroshi Iwakura 和歌山県立医科大学, 医学部, 講師 (20378615)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: グレリン / GPCR / IL-1 / 細胞株 / 分泌調節 / 生合成

Outline of Final Research Achievements

We determined the comprehensive mRNA expression profiles in the ghrelin-producing cell line, MGN3-1 cells. By examining the ligands for the highly expressed GPCR, we found that prostaglandin E2 and tryptophan stimulated ghrelin secretion via EP4 receptor and GPR142, respectively. Except for GPCR, we found that IL-1b significantly suppressed ghrelin mRNA expression in MGN3-1 cells, at least partly through NF-kB pathway. We found that ghrelin-producing cells highly incorporated long-chain fatty acids. The high incorporation of long-chain fatty acids to the cells, which was provided by high levels of Acsl1, contributed to the efficient acylation of ghrelin.

Research Products

• [Journal Article] IL-1β directly suppress ghrelin mRNA expression in ghrelin-producing cells. (2017)
  • Author(s): Bando M, Iwakura H, Ueda Y, Ariyasu H, Inaba H, Furukawa Y, Furuta H, Nishi M, Akamizu T.
  • Journal Title: Mol Cell Endocrinol. Volume: 447 Pages: 45-51
  • DOI: 10.1016/j.mce.2017.02.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Soy-ghretropin, a novel ghrelin-releasing peptide derived from soy protein. (2016)
  • Author(s): Nakato J, Aoki H, Iwakura H, Suzuki H, Kanamoto R, Ohinata K.
  • Journal Title: FEBS Lett. Volume: 590 Issue: 16 Pages: 992-1001
  • DOI: 10.1002/1873-3468.12306
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High incorporation of long-chain fatty acids contributes to the efficient production of acylated ghrelin in ghrelin-producing cells. (2016)
  • Author(s): Bando M, Iwakura H, Koyama H, Hosoda H, Shigematsu Y, Ariyasu H, Akamizu T, Kangawa K, Nakao K.
  • Journal Title: FEBS Lett. Volume: 590 Issue: 7 Pages: 992-1001
  • DOI: 10.1002/1873-3468.12132
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus. (2016)
  • Author(s): Iwakura H, Dote K, Bando M, Koyama H, Hosoda K, Kangawa K, Nakao K
  • Journal Title: PLoS One Volume: 11 Issue: 2 Pages: e0148639-e0148639
  • DOI: 10.1371/journal.pone.0148639
  • NAID: 120005763397
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comprehensive Profiling of GPCR Expression in Ghrelin-producing Cells. (2016)
  • Author(s): Koyama H, Iwakura H, Dote K, Bando M, Hosoda H, Ariyasu H, Kusakabe T, Son C, Hosoda K, Akamizu T, Kangawa K, Nakao K.
  • Journal Title: Endocrinology Volume: 157 Issue: 2 Pages: 692-704
  • DOI: 10.1210/en.2015-1784
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The regulation of circulating ghrelin — with recent updates from cell-based assays [Review] (2015)
  • Author(s): Iwakura H, Kangawa K, Nakao K.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 107-122
  • DOI: 10.1507/endocrj.EJ14-0419
  • NAID: 130004694065
  • ISSN: 0918-8959, 1348-4540
• [Journal Article] Nutrients Differentially Regulate Nucleobindin-2/Nesfatin-1 In Vitro in Cultured Stomach Ghrelinoma (MGN3-1) Cells and In Vivo in Male Mice. (2014)
  • Author(s): Mohan H, Ramesh N, Mortazavi S, Le A, Iwakura H, Unniappan S.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e115102-e115102
  • DOI: 10.1371/journal.pone.0115102
  • Peer Reviewed / Open Access
• [Journal Article] Reduction in circulating ghrelin concentration after maturation does not affect food intake (2014)
  • Author(s): Ariyasu H, Yamada G, Iwakura H, Matsumura S, Inoue K, Kangawa K, Nakao K, Akamizu T
  • Journal Title: Endocrine Journal Volume: 61 Issue: 10 Pages: 1041-1052
  • DOI: 10.1507/endocrj.EJ14-0255
  • NAID: 130004704359
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis (2014)
  • Author(s): Ariyasu H, Iwakura H, Yukawa N, Murayama T, Yokode M, Tada H, Yoshimura K, Teramukai S, Ito T, Shimizu A, Yonezawa A, Kangawa K, Mimori T, Akamizu T
  • Journal Title: Endocrine Journal Volume: 61 Issue: 7 Pages: 735-742
  • DOI: 10.1507/endocrj.EJ14-0088
  • NAID: 130004443975
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] 摂食調節因子産生細胞株 (2014)
  • Author(s): 岩倉 浩, 中尾 一和
  • Journal Title: 日本臨床 Volume: 72 Pages: 94-98
• [Presentation] 細胞系樹立によるグレリン生合成、分泌調節機構の検討 (2016)
  • Author(s): 岩倉 浩、坂東美佳、小山博之、細田洋司、有安宏之、寒川賢治、中尾一和、赤水尚史
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京コンベンションホール
  • Year and Date: 2016-12-16
  • Invited
• [Presentation] 摂食促進因子グレリンの産生と機能の研究 (2016)
  • Author(s): 岩倉 浩
  • Organizer: 第37回日本肥満学会総会
  • Place of Presentation: 東京ファッションタウン
  • Year and Date: 2016-10-07
• [Presentation] GPCR発現プロファイル解析に基づく摂食促進ホルモン、グレリン分泌調節機構の解明 (2015)
  • Author(s): 小山 博之, 岩倉 浩, 坂東 美佳, 細田 洋司, 細田 公則, 寒川 賢治, 中尾 一和
  • Organizer: 第36回日本肥満学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-03
• [Presentation] グレリン産生におけるLPSの直接作用の検討 (2015)
  • Author(s): 坂東 美佳, 岩倉 浩, 小山 博之, 寒川 賢治, 中尾 一和
  • Organizer: 第36回日本肥満学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-03
• [Presentation] ベータトロフィンのノックアウトラット開発とその糖脂質代謝調節における意義の解明 (2015)
  • Author(s): 泉 諒太, 日下部 徹, 野口 倫生, 岩倉 浩, 小山 博之, 坂東 美佳, 宮澤 崇, 寒川 賢治, 中尾 一和
  • Organizer: 第36回日本肥満学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-03
• [Presentation] グレリン細胞における脂肪酸輸送・代謝の検討 (2014)
  • Author(s): 坂東 美佳、岩倉 浩, 小山 博之, 赤水 尚史, 寒川 賢治, 中尾 一和
  • Organizer: 第35回日本肥満学会総会
  • Place of Presentation: シーガイアコンベンションセンター
  • Year and Date: 2014-10-24 – 2014-10-25