Roles for monoacylglycerol lipase in lipid homoestasis

• Project/Area Number: 15K08296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Kita Yoshihiro 東京大学, 大学院医学系研究科(医学部), 准教授 (20401028)
• Co-Investigator(Renkei-kenkyūsha): TOKUOKA Suzumi. M. 東京大学, 大学院医学系研究科, 特任助教 (60511376) ; HAMANO Fumie 国立研究開発法人国立国際医療研究センター, 上級研究員 (80548511)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脂質ホメオスタシス / エネルギー代謝 / 肥満 / モノアシルグリセロールリパーゼ

Outline of Final Research Achievements

We evaluated the role(s) for monoacylglycerol lipase (MGL) in energy homeostasis, using MGL- deficient mice and CB1-MGL double-deficient mice. MGL-deficient mice showed delayed intestinal lipid absorption, which was completely CB1-independent, as CB1-MGL deficient mice but not CB1-single deficient mice showed a similar phenotype. Both MGL-deficient mice and CB1-MGL double-deficient mice, but not CB1-single deficient mice showed strong suppression in feeding behavior after lipid gavage. This phenotype was partially rescued by vagotomy, suggesting MGL's role in satiety regulation through gut-brain axis.

Research Products

• [Journal Article] Relief from neuropathic pain by blocking of platelet-activating factor-pain loop. (2017)
  • Author(s): Shindou, H., Shiraishi, S., Tokuoka, S. M., Takahashi, Y., Harayama, T., Abe, T., Bando, K., Miyano, K., Kita, Y., Uezono, Y., Shimizu, T.
  • Journal Title: FASEB J Volume: - Issue: 7 Pages: 2973-2980
  • DOI: 10.1096/fj.201601183r
  • Peer Reviewed / Open Access
• [Journal Article] LPAAT3 incorporates docosahexaenoic acid into skeletal muscle cell membranes and is upregulated by PPARδ activation (2017)
  • Author(s): Valentine William J.、Tokuoka Suzumi M.、Hishikawa Daisuke、Kita Yoshihiro、Shindou Hideo、Shimizu Takao
  • Journal Title: Journal of Lipid Research Volume: 59 Issue: 2 Pages: 184-194
  • DOI: 10.1194/jlr.m077321
  • Peer Reviewed / Open Access
• [Journal Article] Mediator lipidomics by liquid chromatography-tandem mass spectrometry (2017)
  • Author(s): Yoshihiro Kita, Suzumi M. Tokuoka, Takao Shimizu
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Volume: 印刷中 Issue: 8 Pages: 777-781
  • DOI: 10.1016/j.bbalip.2017.03.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Imaging of Intracellular Fatty Acids by Scanning X-ray Fluorescence Microscopy. (2016)
  • Author(s): Shimura, M., Shindou, H, Szyrwiel, L., Tokuoka, M.S., Hamano, F., Matsuyama, S., Okamoto, M., Matsunaga, A., Kita, Y., Ishizaka, Y., Yamauchi, K., Komura, Y., Lobinski, R., Shimizu, I., Shimizu, T. *, equal contribution
#, equal corresponding author
  • Journal Title: FASEB J. Volume: 30 Issue: 12 Pages: 4149-4158
  • DOI: 10.1096/fj.201600569r
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fever is mediated by conversion of endocannabinoid 2-arachidonoylglycerol to prostaglandin E₂ (2015)
  • Author(s): Yoshihiro Kita, Kenij Yoshida, Suzumi M. Tokuoka, Fumie Hamano, Maya Yamazaki, Kenji Sakimura, Masanobu Kano, Takao Shimizu
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133663-e0133663
  • DOI: 10.1371/journal.pone.0133663
  • Peer Reviewed / Open Access
• [Presentation] モノアシルグリセロールリパーゼによる脂質ホメオスタシスの制御 (2015)
  • Author(s): 北 芳博、吉田憲司、徳岡涼美、浜野文三江、崎村建司、 狩野方伸、清水孝雄
  • Organizer: 第38回日本分子生物学会年会／第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-03