Screening of the food molecules to control incretin-signalin with novel mode of action

• Project/Area Number: 17K07794
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Saga University
• Principal Investigator: Mitsutake Susumu 佐賀大学, 農学部, 准教授 (10344475)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: sphingolipid / sphingoid base / GPR120 / incretin / phytosphingosine / インクレチン / T1R2 / T1R3 / 栄養学

Outline of Final Research Achievements

In this study, we aimed to elucidate how the food molecules affect incretin signaling. I applied the TGFα-shedding assay to the GPR120 and established a highly quantitative detection method. Using this method, we discovered that phtosphingosine (PHS), which is abundant in yeast cell membranes, is a novel ligand for GPR120. Additionally, we found that the polyphenols contained in black tea (microorganism fermented tea) could be new ligands for GPR120. Both of the molecules are increased in food by microbial fermentation. These studies are interesting, and show new food function of fermented foods.

Academic Significance and Societal Importance of the Research Achievements

GPR120/インクレチンシグナリングは、元来、高エネルギー分子である脂肪酸の摂取に応答し、過剰なエネルギー摂取を抑制する為に、インスリンの分泌や食欲抑制といった生体応答を引き起こす。一方PHSは、小腸から吸収されずエネルギーとはなりにくい事が知られている。我々の発見は、ヒトが高エネルギー分子である脂肪酸を摂取せずに、非栄養成分であるPHSを介して抗肥満システムを惹起し、生体恒常性の維持／肥満・２型糖尿病の予防を行ってきた可能性を示している。これらが日本の伝統的な発酵食品中から見つかった事から、発酵食品の新たな食品機能性を示唆しており、社会的意義を持つ研究へ発展する事が期待される。

Research Products

• [Journal Article] Kondjac ceramide (kier) regulates keratinocyte migration by sema3A-like repulsion mechanism (2019)
  • Author(s): Usuki, N. Tamura, T. Tamura, S. Higashiyama, K. Tanji, S. Mitsutake, A. Inoue, J. Aoki, K. Mukai, Y. Igarashi
  • Journal Title: Biochemistry and Biophysics Reports Volume: 17 Pages: 132-138
  • DOI: 10.1016/j.bbrep.2018.11.004
  • Peer Reviewed
• [Journal Article] Koji glycosylceramide commonly contained in Japanese traditional fermented foods alters cholesterol metabolism in obese mice (2018)
  • Author(s): Hamajima Hiroshi、Tanaka Masaru、Miyagawa Miyuki、Sakamoto Mayuko、Nakamura Tsuyoshi、Yanagita Teruyoshi、Nishimukai Megumi、Mitsutake Susumu、Nakayama Jiro、Nagao Koji、Kitagaki Hiroshi
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: - Issue: 8 Pages: 1-9
  • DOI: 10.1080/09168451.2018.1562877
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The fungal 9-methylsphingadiene is a novel ligand for both PPARg and GPR120 (2018)
  • Author(s): S. Esaki, T. Nagasawa, H. Tanaka, A. Tomonaga, D. Mikami, S. Usuki, H. Hamajima, S. Sakai, Y. Hama, Y. Igarashi, H. Kitagaki, S. Mitsutake*
  • Journal Title: J. Food Biochem. Volume: なし Issue: 5 Pages: e12624-e12624
  • DOI: 10.1111/jfbc.12624
  • Peer Reviewed
• [Journal Article] Structure-inspired design of a sphingolipid mimic sphingosine-1-phosphate receptor agonist from a naturally occurring sphingomyelin synthase inhibitor (2018)
  • Author(s): M.M.M. Swamy, Y Murai, Y Ohno, K Jojima, A Kihara, S Mitsutake, Y Igarashi, J Yu, M Yao, Y Suga, M Anetai and K Monde
  • Journal Title: Chem. Commun. Volume: 54 Issue: 90 Pages: 12758-12761
  • DOI: 10.1039/c8cc05595e
  • NAID: 120006767539
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multiple roles of SMS2 in white and brown adipose tissues form diet-induced obese mice (2018)
  • Author(s): H. Hamamatsu, S. Mitsutake, S. Sakai, T. Okazaki, K. Watanabe, Y. Igarashi, K. Yuyama
  • Journal Title: J. Metabolic Syndrome Volume: 7 Issue: 02 Pages: 241-241
  • DOI: 10.4172/2167-0943.1000241
  • Peer Reviewed / Open Access
• [Journal Article] Phytosphingosine is a novel activator of GPR120 (2018)
  • Author(s): Nagasawa Tomotaka、Nakamichi Hikaru、Hama Yoichiro、Higashiyama Shigeki、Igarashi Yasuyuki、Mitsutake Susumu
  • Journal Title: Journal of Biochemistry Volume: - Issue: 1 Pages: 27-32
  • DOI: 10.1093/jb/mvy017
  • NAID: 40021625289
  • Peer Reviewed
• [Journal Article] Sphingomyelin in microdomains of the plasma membrane regulates amino acid-stimulated mTOR signal activation (2018)
  • Author(s): Zama Kota、Mitsutake Susumu、Okazaki Toshiro、Igarashi Yasuyuki
  • Journal Title: Cell Biology International Volume: - Issue: 7 Pages: 823-831
  • DOI: 10.1002/cbin.10941
  • Peer Reviewed
• [Presentation] theaflavin-3,3'-digallateは長鎖脂肪酸受容体GPR120活性化に影響を与える (2019)
  • Author(s): 長澤智隆、東山繁樹、濱洋一郎、光武進
  • Organizer: 第42回 日本分子生物学会年会
• [Presentation] 食品由来非栄養成分による脂肪酸受容体GPR120活性化制御メカニズムの解明 (2019)
  • Author(s): 長澤智隆、中道ひかる、東山繁樹、濱洋一郎、光武進
  • Organizer: 日本脂質生化学大会
• [Presentation] Dynamic modification of Sphingolipids Regulate Function of the Plasma Membrane (2017)
  • Author(s): Susumu Mitsutake
  • Organizer: 2017 International Conference Korean Society for Molecular and Cellular Biology
  • Int'l Joint Research / Invited