Physiological regulation of adipose tissue browning by prostaglandin receptors

• Project/Area Number: 18K14904
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• 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)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: プロスタグランジン / 受容体 / 脂肪分解 / 熱産生 / 脂肪組織 / 脂質代謝 / Browning / プロスタグランジン受容体

Outline of Final Research Achievements

In this study, we revealed that prostaglandin (PG) E2 promotes lipolysis in white adipose tissue via EP4 receptor by counteracting insulin signaling, and regulates lipid homeostasis and thermogenesis. Moreover, we found that this receptor modulates the quality of adipose tissue such as fibrosis and the capacity of lipid storage by stimulating collagen production.

Academic Significance and Societal Importance of the Research Achievements

本研究により、プロスタグランジン受容体による生体内の脂質代謝調節機構の一端が明らかとなった。また、今回の研究結果はマウスだけでなく、ヒトのSNPs解析においても再現されており、本研究で得られた知見を肥満や糖尿病、脂肪肝といった生活習慣病の治療や予防に応用できれば、その社会的意義は大きい。

Research Products

• [Journal Article] Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice (2020)
  • Author(s): Razali N, Hohjoh H, Inazumi T, Maharjan BD, Nakagawa K, Konishi M, Sugimoto Y, Hasegawa H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 43 Issue: 4 Pages: 649-662
  • DOI: 10.1248/bpb.b19-00838
  • NAID: 130007825267
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2020-04-01
  • Peer Reviewed
• [Journal Article] Prostaglandin E2-EP4 axis promotes lipolysis and fibrosis in adipose tissue leading to ectopic fat deposition and insulin resistance. (2020)
  • Author(s): Inazumi T, Yamada K, Shirata N, Sato H, Taketomi Y, Morita K, Hohjoh H, Tsuchiya S, Oniki K, Watanabe T, Sasaki Y, Oike Y, Ogata Y, Saruwatari J, Murakami M, Sugimoto Y.
  • Journal Title: Cell Rep. Volume: 33 Issue: 2 Pages: 108265-108265
  • DOI: 10.1016/j.celrep.2020.108265
  • Peer Reviewed / Open Access
• [Journal Article] Advanced oxidation protein products contribute to renal tubulopathy via perturbation of renal fatty acids (2020)
  • Author(s): Imafuku, T., Watanabe, H., Satoh, T., Matsuzaka, T., Inazumi, T., Kato, H., Tanaka, S., Nakamura, Y., Nakano, T., Tokumaru, K., Maeda, H., Tanaka, M., Matsushita, K., Tsuchiya, S., Sugimoto, Y., Shimano, H., Fukagawa, M., and Maruyama, T.
  • Journal Title: Kidney360 Volume: 1 Issue: 8 Pages: 781-796
  • DOI: 10.34067/kid.0000772019
  • Peer Reviewed / Open Access
• [Journal Article] Effects of the selective EP2 receptor agonist omidenepag on adipocyte differentiation in 3T3-L1 cells (2020)
  • Author(s): Yamamoto Y, Taniguchi T, Inazumi T, Iwamura R, Yoneda K, Odani-Kawabata N, Matsugi T, Sugimoto Y, Shams NK.
  • Journal Title: Journal of Ocular Pharmacology and Therapeutics Volume: 36 Issue: 3 Pages: 162-169
  • DOI: 10.1089/jop.2019.0079
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases. (2019)
  • Author(s): Tsuge K, Inazumi T, Shimamoto A, Sugimoto Y.
  • Journal Title: Int Immunol Volume: 印刷中 Issue: 9 Pages: 1-10
  • DOI: 10.1093/intimm/dxz021
  • Peer Reviewed / Open Access
• [Journal Article] Essential role of prostaglandin E2 and the EP3 receptor in lymphatic vessel development during zebrafish embryogenesis (2019)
  • Author(s): Iwasaki R, Tsuge K, Kishimoto K, Hayashi Y, Iwaana T, Hohjoh H, Inazumi T, Kawahara A, Tsuchiya S, Sugimoto Y.
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 7650-7650
  • DOI: 10.1038/s41598-019-44095-5
  • Peer Reviewed / Open Access
• [Journal Article] Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface (2019)
  • Author(s): Toyoda Y, Morimoto K, Suno R, et al.
  • Journal Title: Nature Chemical Biology Volume: 15 Issue: 1 Pages: 18-26
  • DOI: 10.1038/s41589-018-0131-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] プロスタグランジン受容体による脂質恒常性の調節機構. (2020)
  • Author(s): 稲住知明、杉本幸彦
  • Organizer: 第93回 日本薬理学会年会
  • Invited
• [Presentation] 複数の受容体を介したプロスタグランジンの着床制御機構. (2019)
  • Author(s): 稲住知明、大窪喜丸、馬驍彦、大塚友絵、杉本聡子、土屋創健、竹尾透、中潟直己、杉本幸彦
  • Organizer: 第92回日本生化学会大会
• [Presentation] The role of multiple prostanoid receptors in embryo implantation and spacing. (2019)
  • Author(s): Inazumi T, Okubo K, Xiaoyen Ma, Otsuka T, Hirai Y, Sugimoto T, Tsuchiya S, Takeo T, Nakagata N, Sugimoto Y.
  • Organizer: 60th International Conference on the Bioscience of Lipids.
  • 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機構 (2018)
  • Author(s): 稲住知明、山田清隆、土屋創健、猿渡淳二、成宮周、杉本幸彦
  • Organizer: 第40回生体膜と薬物の相互作用シンポジウム
• [Presentation] プロスタグランジンEP4受容体は生理的な脂肪細胞機能を調節する (2018)
  • Author(s): 稲住知明、山田清隆、土屋創健、猿渡淳二、成宮周、杉本幸彦
  • Organizer: 第91回日本生化学会
• [Remarks] 熊本大学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