Studies on molecular mechanisms of brown adipocyte for controlling obesity.

• Project/Area Number: 17K17254
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: OUE KANA 広島大学, 病院(歯), 助教 (60760329)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 褐色脂肪細胞 / エネルギー代謝 / UCP1 / 肥満 / ＵＣＰ１

Outline of Final Research Achievements

PLC-related catalytically inactive protein (PRIP) gene-knockout (Prip-KO) mice exhibit obesity resistance. In this study, we analyzed the molecular mechanism of PRIP-related regulation of energy metabolism. Prip-KO mice showed increased energy production mediated by uncoupling protein 1 (UCP1) in brown adipocytes. Moreover, it was suggested that PRIP also affects the browning of subcutaneous white adipose tissue under cold environment.
This study demonstrated that PRIP regulates energy metabolism in white adipocyte and brown adipocyte, and propose PRIP as a new therapeutic target for controlling obesity or developing novel anti-obesity drugs.

Academic Significance and Societal Importance of the Research Achievements

PRIPは、白色脂肪細胞だけでなく褐色脂肪細胞においても脂肪分解を制御しており、UCP1の活性化や遺伝子発現の調節に関与していた。本研究により、褐色脂肪細胞におけるPRIPが仲介するエネルギー代謝の分子基盤の一部が明らかとなり、エネルギー代謝調節機構の解明に繋がった。
今後、本研究をさらに深め、PRIPが仲介する褐色脂肪細胞の脂肪分解やエネルギー代謝機構を制御できれば、白色脂肪細胞の脂肪蓄積を抑制しその余剰脂肪酸を褐色脂肪細胞でエネルギーとして放出させるような新薬の開発にも繋がると期待できる。そして、PRIPを介した新たな肥満の予防策や治療戦略に通じると考える。

Research Products

• [Journal Article] Phospholipase C-related catalytically inactive protein regulates lipopolysaccharide-induced hypothalamic inflammation-mediated anorexia in mice (2019)
  • Author(s): Yamawaki Yosuke、Shirawachi Satomi、Mizokami Akiko、Nozaki Kanako、Ito Hikaru、Asano Satoshi、Oue Kana、Aizawa Hidenori、Yamawaki Shigeto、Hirata Masato、Kanematsu Takashi
  • Journal Title: Neurochemistry International Volume: 131 Pages: 104563-104563
  • DOI: 10.1016/j.neuint.2019.104563
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-related catalytically inactive protein: A novel signaling molecule for modulating fat metabolism and energy expenditure (2019)
  • Author(s): Kanematsu T, Oue K, Okumura T, Harada K, Yamawaki Y, Asano S, Mizokami A, Irifune M, Hirata M
  • Journal Title: J Oral Biosci Volume: 61(2) Issue: 2 Pages: 65-72
  • DOI: 10.1016/j.job.2019.04.002
  • Peer Reviewed / Open Access
• [Journal Article] Chronic cold exposure enhances the induction of uncoupling protein 1 in adipose tissues of phospholipase C-related catalytically inactive protein-knockout mice (2017)
  • Author(s): Kana Oue, Yosuke Yamawaki, Satoshi Asano, Mizokami Akiko, Masato Hirata, Masahiro Irifune, Takashi Kanematsu
  • Journal Title: Ｊｏｕｒｎａｌ ｏｆ Ｏｒａｌ Ｂｉｏｓｃｉｅｎｃｅｓ Volume: 59 Pages: 108-112
  • Peer Reviewed / Open Access
• [Journal Article] General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice. (2017)
  • Author(s): Hayashiuchi M, Kitayama T, Morita K, Yamawaki Y, Oue K, Yoshinaka T, Asano S, Harada K, Kang Y, Hirata M, Irifune M, Okada M, Kanematsu T.
  • Journal Title: Journal of Anesthesia Volume: in press Issue: 4 Pages: 531-538
  • DOI: 10.1007/s00540-017-2350-2
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation. (2017)
  • Author(s): Yamawaki Y, Oue K, Shirawachi S, Asano S, Harada K, Kanematsu T.
  • Journal Title: Japanese Dental Science Review Volume: 53（1） Issue: 1 Pages: 18-24
  • DOI: 10.1016/j.jdsr.2016.06.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 肥満制御研究の新潮流 白色・褐色脂肪細胞の機能を制御しエネルギー代謝を調節する新しい分子基盤 (2018)
  • Author(s): 兼松 隆，大植香菜, 山脇洋輔, 浅野智志
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] 寒冷刺激で見られるPRIP遺伝子欠損マウスのUCP1発現の亢進 (2017)
  • Author(s): 大植香菜, 入舩正浩, 兼松 隆
  • Organizer: 第131回日本薬理学会近畿部会
• [Presentation] The mechanism of phospholipase C-related catalytically inactive protein (PRIP)-mediated energy metabolism by β-adrenergic stimulation in brown adipocytes (2017)
  • Author(s): Kana Oue, Yosuke Yamawaki, Satoshi Asano, Masahiro Irifune, Takashi Kanematsu
  • Organizer: 第59回歯科基礎医学会学術集会