Role of prostaglandin signaling in the control of glucose homeostasis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08230
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kyoto University
• Principal Investigator: YOKODE MASAYUKI 京都大学, 医学研究科, 教授 (20252447)
• Co-Investigator(Kenkyū-buntansha): 南 学 京都大学, 医学研究科, 准教授 (90511907)
• Co-Investigator(Renkei-kenkyūsha): KAMEI Kaeko 京都工芸繊維大学, 工芸科学研究科, 教授 (00214544)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: プロスタグランジン / マクロファージ / 慢性炎症 / 糖代謝

Outline of Final Research Achievements

With increasing body weight, macrophages accumulate in adipose tissue, giving rise to chronic inflammation and insulin resistance. In this study, we treated db/db mice with a prostaglandin E2 type 4 receptor (EP4) -selective agonist to explore the role of EP4 signaling in obesity-related inflammation. In the EP4 agonist-treated group, glucose tolerance and insulin resistance were significantly improved. Administration of the EP4 agonist inhibited the accumulation of F4/80-positive macrophages and the formation of crown-like structures, but increased the number of anti-inflammatory M2 macrophages in adipose tissue. In vitro M1/M2 polarization assay showed that treatment with EP4 agonist enhanced M2 polarization in wild-type peritoneal macrophages, whereas EP4-deficient macrophages were less susceptible to M2 polarization. Thus, EP4 signaling plays a critical role in obesity-related adipose tissue inflammation by regulating macrophage recruitment and polarization.

Free Research Field

先端医療構築学、内科学、老年医学