Analyses of regulatory mechanisms of energy homeostasis via free fatty acids receptors

• Project/Area Number: 15H05652
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Atsuhiko Ichimura 京都大学, 薬学研究科, 特定助教 (10609209)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2016: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 脂肪酸 / 受容体 / GPCR / エネルギー代謝 / 肥満 / 糖尿病 / 脂肪酸受容体 / 遊離脂肪酸 / 生体分子 / 薬理学 / 薬学 / 脂質 / ゲノム / ゲノム薬理学 / 分子薬理学 / 遺伝子多型 / 代謝異常 / 栄養学

Outline of Final Research Achievements

In this study, we aimed to elucidate the physiological functions of fatty acid receptors responsible for sensing and controlling energy metabolism. Among fatty acid receptors, we focused on GPR 120, which is a medium long-chain free fatty acid receptor, and attempted to create tissue-specific gene deficient mice to elucidate tissue-specific physiological functions. As a result, we shave generated GPR 120 floxed mouse with LoxP sequence inserted with exon 1 of GPR 120 genomic sequences. We also have successfully obtained GPR120 systemic deficient mice by crossing GPR120 floxed mice with systemic Cre expressing mice. In the future, further research development is expected through acquisition and analysis of deficient mice in various adipose tissues and monocytes in progress.

Research Products

• [Journal Article] The natural flavonoid myricetin inhibits gastric H + , K + -ATPase (2018)
  • Author(s): Miyazaki Yuu、Ichimura Atsuhiko、Sato Shun、Fujii Takuto、Oishi Shinya、Sakai Hideki、Takeshima Hiroshi
  • Journal Title: European Journal of Pharmacology Volume: 820 Pages: 217-221
  • DOI: 10.1016/j.ejphar.2017.12.042
  • Peer Reviewed
• [Journal Article] Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1 (2018)
  • Author(s): Kawaguchi Shin-Ichi, Gonda Yuhei, Yamamoto Takuya, Sato Yuki, Shinohara Hiroyuki, Kobiki Yohsuke, Ichimura Atsuhiko, Dan Takashi, Sonoda Motohiro, Miyata Toshio, Ogawa Akiya, Tsujita Tadayuki
  • Journal Title: Molecules Volume: 23 Issue: 4 Pages: 885-885
  • DOI: 10.3390/molecules23040885
  • Peer Reviewed / Open Access
• [Journal Article] <i><b>Gm7325</b></i><b> is MyoD-dependently expressed in activated muscle satellite </b><b>cells </b> (2017)
  • Author(s): Takei D, Nishi M, Fukada S, Doi M, Okamura H, Uezumi A, Zhang L, Yoshida M, Miyazato M, Ichimura A, Takeshima H.
  • Journal Title: Biomedical Research Volume: 38 Issue: 3 Pages: 215-219
  • DOI: 10.2220/biomedres.38.215
  • NAID: 130006865614
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. (2017)
  • Author(s): Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B.
  • Journal Title: FASEB Journal Volume: - Issue: 6 Pages: 2625-2637
  • DOI: 10.1096/fj.201600871rr
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polymorphic Variation in FFA Receptors: Functions and Consequences. (2017)
  • Author(s): Ichimura A.
  • Journal Title: Handbook of Experimental Pharmacology Volume: 236 Pages: 133-158
  • DOI: 10.1007/164_2016_57
  • ISBN: 9783319506920, 9783319506937
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization. (2016)
  • Author(s): C.Zhao, A.Ichimura, N.Qian, T.Iida, D.Yamazaki, N.Noma, M.Asagiri, K.Yamamoto, S.Komazaki, C.Sato, F.Aoyama, A.Sawaguchi, S.Kakizawa, M.Nishi, and H.Takeshima.
  • Journal Title: science signaling Volume: 9 Issue: 428
  • DOI: 10.1126/scisignal.aad9055
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRIC-B Mutations Causing Osteogenesis Imperfecta. (2016)
  • Author(s): Ichimura A, Takeshima H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Pages: 1743-1747
  • NAID: 130005268698
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nutritional Signaling via Free Fatty Acid Receptors (2016)
  • Author(s): J. Miyamoto, S. Hasegawa, M. Kasubuchi, A. Ichimura, A. Nakajima, and I. Kimura
  • Journal Title: Int J Mol Sci Volume: 17 Issue: 4 Pages: 450-450
  • DOI: 10.3390/ijms17040450
  • NAID: 120005947125
  • Peer Reviewed / Open Access
• [Journal Article] Mitsugumin 56 (hedgehog acyltransferase-like) is a sarcoplasmic reticulum-resident protein essential for postnatal muscle maturation. (2015)
  • Author(s): Van B, Nishi M, Komazaki S, Ichimura A, Kakizawa S, Nakanaga K, Aoki J, Park KH, Ma J, Ueyama T, Ogata T, Maruyama N, Takeshima H.
  • Journal Title: FEBS Lett. Volume: in press Issue: 10 Pages: 1095-1104
  • DOI: 10.1016/j.febslet.2015.03.028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. (2015)
  • Author(s): Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I.
  • Journal Title: Nutrients Volume: 7 Issue: 4 Pages: 2839-2849
  • DOI: 10.3390/nu7042839
  • NAID: 120005663309
  • Peer Reviewed
• [Journal Article] Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis. (2015)
  • Author(s): Pelisch N, Dan T, Ichimura A, Sekiguchi H, Vaughan DE, van Ypersele de Strihou C, Miyata T.
  • Journal Title: PloS One Volume: 10 Issue: 4 Pages: e0124510-e0124510
  • DOI: 10.1371/journal.pone.0124510
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity. (2015)
  • Author(s): Placencio VR, Ichimura A, Miyata T, DeClerck YA.
  • Journal Title: PloS One Volume: 10 Issue: 7 Pages: e0133786-e0133786
  • DOI: 10.1371/journal.pone.0133786
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Editorial: Obesity and Diabetes: Energy Regulation by Free Fatty Acid Receptors. (2015)
  • Author(s): Ichimura A, Kimura I.
  • Journal Title: Front Endocrinology Volume: 6 Pages: 178-178
  • DOI: 10.3389/fendo.2015.00178
  • NAID: 120005946997
  • Peer Reviewed / Open Access
• [Presentation] Spontaneous Ca2+ fluctuations mediated by TRPM7 channels in growth plate chondrocytes (2018)
  • Author(s): Nianchao Qian, Atsuhiko Ichimura, Daisuke Takei, Hua Zhu, Miyuki Nishi, Hiroshi Takeshima,
  • Organizer: Biophysical society 62nd Annual Meeting
  • Int'l Joint Research
• [Presentation] フラボノイドミリセチンは胃のH+, K+-ATPaseを抑制する (2018)
  • Author(s): 宮崎侑, 市村敦彦, 佐藤駿, 藤井拓人, 大石真也、酒井秀紀、竹島浩
  • Organizer: 日本薬学会 第138回年会
• [Presentation] TRIC-Bチャネルの骨形成と破骨細胞における生理機能の解析 (2016)
  • Author(s): 銭年超, 市村敦彦, 朝霧成挙, 竹島浩
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-03-26
• [Presentation] TRIC-Bチャネルの骨形成と骨芽細胞における生理機能の解析 (2016)
  • Author(s): 趙成珠, 市村敦彦, 山本浩司, 竹島浩
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-03-26
• [Presentation] Drug development of Plasminogen Activator Inhibitor 1 (PAI-1) inhibitor (2015)
  • Author(s): 市村敦彦
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 甲府市総合市民会館
  • Year and Date: 2015-05-21
  • Invited
• [Remarks] 市村敦彦 特定助教（京都大学大学院薬学研究科）の共著論文がMoleculesにて公開されました。
  • URL: http://k-connex.kyoto-u.ac.jp/ja/news/3515.html
• [Remarks] http://k-connex.kyoto-u.ac.jp/ja/news/3212.html
  • URL: http://k-connex.kyoto-u.ac.jp/ja/news/3212.html
• [Remarks] K-CONNEX 研究者紹介 市村 敦彦
  • URL: http://k-connex.kyoto-u.ac.jp/ja/researcher/atsuhiko-ichimura
• [Remarks] K-CONNEX Dr. Atsuhiko ICHIMURA
  • URL: http://k-connex.kyoto-u.ac.jp/en/researcher/atsuhiko-ichimura