Physiological regulation of lipid homeostasis by prostaglandin EP4 receptor

• Project/Area Number: 15K18875
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Inazumi Tomoaki 熊本大学, 大学院生命科学研究部(薬), 助教 (80746503)
• Research Collaborator: YAMADA Kiyotaka
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: プロスタグランジン受容体 / 脂質代謝

Outline of Final Research Achievements

In this study, we found that prostaglandin (PG) E2-EP4 receptor pathway regulates physiological lipid distribution by changing the lipid accumulation balance between adipose tissue and liver. Adipocyte-specific EP4 KO mice showed increased adiposity like in global KO mice, suggesting that PGE2 mainly acts on EP4 receptor in adipocyte. Moreover, EP4 agonist treatment to diet-induced obesity mice changed the lipid distribution in several tissues. These results show the possibility that EP4 receptor may be useful as a therapeutic target of dyslipidemia.

Research Products

• [Journal Article] An aromatic amino acid within intracellular loop 2 of the prostaglandin EP2 receptor is a prerequisite for selective association and activation of Gαs. (2017)
  • Author(s): Yano A, Takahashi Y, Moriguchi H, Inazumi T, Koga T, Otaka A, Sugimoto Y.
  • Journal Title: Biochim Biophys Acta Mol Cell Biol Lipids Volume: 1862 Issue: 6 Pages: 615-622
  • DOI: 10.1016/j.bbalip.2017.03.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of prostaglandin receptors in female reproduction. (2015)
  • Author(s): Sugimoto Y, Inazumi T, Tsuchiya S
  • Journal Title: J Biochem Volume: 157 Issue: 2 Pages: 73-80
  • DOI: 10.1093/jb/mvu081
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 脂質代謝におけるプロスタグランジンEP4受容体の生理機能解析 (2017)
  • Author(s): 稲住知明、山田清隆、土屋創健、成宮周、杉本幸彦
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] Prostaglandin E2 regulates physiological lipid storage status. (2017)
  • Author(s): Sugimoto, Y., Inazumi, T., Tsuchiya, S., Narumiya, S.
  • Organizer: The 15th International Conference on Bioactive Lipids in Inflammation, Cancer and Related Diseases
  • Int'l Joint Research
• [Presentation] Regulation of adipocyte functions by the prostaglandin EP4 receptor. (2017)
  • Author(s): Sugimoto, Y.
  • Organizer: International Conference on Lipoquality
  • Int'l Joint Research / Invited
• [Presentation] 脂肪組織におけるプロスタグランジンEP4受容体の生理機能解析 (2017)
  • Author(s): 稲住 知明、山田 清隆、土屋 創健、杉本 幸彦
  • Organizer: 平成29年度日本生化学会九州支部例会
• [Presentation] プロスタグランジンEP4受容体による脂質代謝調節機構 (2017)
  • Author(s): 杉本幸彦、稲住知明、山田清隆、土屋創健、猿渡淳二、成宮 周
  • Organizer: 第90回日本内分泌学会
• [Presentation] プロスタグランジンEP4受容体を介した脂質代謝調節機構 (2016)
  • Author(s): 山田 清隆、稲住 知明、土屋 創健、杉本 幸彦
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] Roles of prostaglandin EP4 receptor in adipose tissue. (2016)
  • Author(s): Sugimoto, Y., Inazumi, T., Tsuchiya, S., Narumiya, S.
  • Organizer: The 7th International conference on phospholipase A2 and Lipid Mediators(PLM2016)
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-19
  • Int'l Joint Research
• [Presentation] プロスタグランジンEP4受容体による脂肪細胞機能の調節 (2015)
  • Author(s): 稲住知明、土屋創健、猿渡淳二、中川和子、成宮周、杉本幸彦
  • Organizer: 第88回日本生化学会大会（BMB2015）
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Prostaglandin E2 contributes lipid homeostasis in adipose tissue. (2015)
  • Author(s): Inazumi, T., Tsuchiya, S., Narumiya, S., Sugimoto, Y.
  • Organizer: International Symposium on Chronic Inflammatory Diseases, Kumamoto
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Book] Bioactive Lipid Mediators: Current Reviews and Protocols (2015)
  • Author(s): Tomoaki Inazumi, Yukihiko Sugimoto
  • Total Pages: 426
  • Publisher: Springer
• [Remarks] 熊本大学大学院生命科学研究部薬学生化学分野ホームページ
  • URL: http://www.pharm.kumamoto-u.ac.jp/Labs/seika/index.html