The odd chain fatty acids (OCFAs) is a new anti-inflammatory agent

• Project/Area Number: 16H05898
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Eating habits
• Research Institution: Aichi Medical University (2017-2019); University of Shizuoka (2016)
• Principal Investigator: Tomono Susumu 愛知医科大学, 医学部, 助教 (60554011)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000); Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: 機能性脂質 / 抗炎症 / 奇数鎖脂肪酸 / 抗炎症作用 / LC/MS / 機能性脂肪酸 / Acyl Biotin exchange / 炎症 / 生活習慣病 / 脂質 / 脂肪酸 / クリックケミストリー

Outline of Final Research Achievements

Recently, some large-scale epidemiological studies reported an inverse association between chronic inflammatory diseases including type 2 diabetes risk and odd-chain saturated fatty acids (OCFAs). However, the molecular mechanism by which OCFAs suppress inflammation remains unclear. In this study, we demonstrated that OCFAs (C15:0 and C17:0) regulated the production of proinflammatory cytokine and lipid mediators in macrophages. Furthermore, we found that OCFAs inhibit proinflammatory NFkB signaling through p65 degradation in macrophage. It is expected that a future research through detailed analysis of the OCFAs-target protein in progress.

Academic Significance and Societal Importance of the Research Achievements

糖尿病や心血管疾患、神経変性疾患およびがんに代表される生活習慣病は現在、我が国において死亡者数の約６割、医療費は約３割を占めており、今後さらに進行する高齢化社会における健康寿命の延伸への最大の阻害要因であり、国民医療費負担にも大きな影響を与えている。日々摂取する食品から、機能性成分を見出し、作用機序の解明を試みることは非常に意義のあるものであると考える。本研究で、これまで報告がほとんどなかった奇数鎖脂肪酸の抗炎症作用機序について新たな知見を得たことは生活習慣病を始めとする疾病予防に非常に意義のある研究であると考えられる。

Research Products

• [Journal Article] The Radical Scavenger NZ-419 Suppresses Intestinal Polyp Development in Apc-Mutant Mice (2020)
  • Author(s): Kurokawa Yurie、Fujii Gen、Tomono Susumu、Miyamoto Shingo、Hamoya Takahiro、Takahashi Maiko、Narita Takumi、Komiya Masami、Kobayashi Masaki、Higami Yoshikazu、Mutoh Michihiro
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 1 Pages: 270-270
  • DOI: 10.3390/jcm9010270
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase A2 from bee venom increases poly(I:C)-induced activation in human keratinocytes (2020)
  • Author(s): Nakashima Akina、Tomono Susumu、Yamazaki Tatsuya、Inui Masanori、Morita Naoko、Ichimonji Isao、Takagi Hidekazu、Nagaoka Fumiaki、Matsumoto Misako、Ito Yasuhiko、Yanagishita Takeshi、Miyake Kensuke、Watanabe Daisuke、Akashi-Takamura Sachiko
  • Journal Title: International Immunology Volume: - Issue: 6 Pages: 371-383
  • DOI: 10.1093/intimm/dxaa005
  • Peer Reviewed
• [Journal Article] Clostridium butyricum Modulates the Microbiome to Protect Intestinal Barrier Function in Mice with Antibiotic-Induced Dysbiosis (2020)
  • Author(s): Hagihara M.、Kuroki Y.、Ariyoshi T.、Higashi S.、Fukuda K.、Yamashita R.、Matsumoto A.、Mori T.、Mimura K.、Yamaguchi N.、Okada S.、Nonogaki T.、Ogawa T.、Iwasaki K.、Tomono S.、Asai N.、Koizumi Y.、Oka K.、Yamagishi Y.、Takahashi M.、Mikamo H.
  • Journal Title: iScience Volume: 23 Issue: 1 Pages: 100772-100772
  • DOI: 10.1016/j.isci.2019.100772
  • Peer Reviewed / Open Access
• [Journal Article] Sesame Lignans Suppress Age-Related Cognitive Decline in Senescence-Accelerated Mice (2019)
  • Author(s): Shimoyoshi Satomi、Takemoto Daisuke、Ono Yoshiko、Kitagawa Yoshinori、Shibata Hiroshi、Tomono Susumu、Unno Keiko、Wakabayashi Keiji
  • Journal Title: Nutrients Volume: 11 Issue: 7 Pages: 1582-1582
  • DOI: 10.3390/nu11071582
  • Peer Reviewed
• [Journal Article] Receptor-destroying enzyme (RDE) from Vibrio cholerae modulates IgE activity and reduces the initiation of anaphylaxis (2019)
  • Author(s): Yamazaki Tatsuya、Inui Masanori、Hiemori Keiko、Tomono Susumu、Itoh Makoto、Ichimonji Isao、Nakashima Akina、Takagi Hidekazu、Biswas Mrityunjoy、Izawa Kumi、Kitaura Jiro、Imai Teruko、Sugiura Nobuo、Tateno Hiroaki、Akashi-Takamura Sachiko
  • Journal Title: Journal of Biological Chemistry Volume: 294 Issue: 17 Pages: 6659-6669
  • DOI: 10.1074/jbc.ra118.006375
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Ceramide phosphoethanolamineによるArginase-1発現誘導 (2019)
  • Author(s): 伴野勧、長岡史晃、一文字功、山崎達也、乾匡範、高木秀和、伊藤誠、高村祥子
  • Organizer: 第92回日本生化学会大会
• [Presentation] Ceramide phosphoethanolamine, a sphingomyelin analog prevents NO production in bone marrow-derived macrophages (2019)
  • Author(s): Susumu Tomono, Tatsuya Yamazaki, Masanori Inui, Sachiko Akashi-Takamura.
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] ハチ毒由来のPhospholipase A2 (PLA2) はヒト角化細胞でのPoly(I:C) 活性化を増強させる (2018)
  • Author(s): 中島昭奈、伴野勧、山崎達也、森田奈央子、一文字功、高木秀和、長岡史晃、松本美佐子、乾匡範、柳下武士、渡辺大輔、高村祥子
  • Organizer: 第24回エンドトキシン・自然免疫研究会
• [Presentation] IgE glycosylation is important for the binding to mast cells and allergy induction. (2018)
  • Author(s): Yamazaki T, Inui M, Tomono S, Ichimonji I, Izawa K, Kitaura J, Akashi-Takamura S.
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] Phospholipase A2 from Honey Bee Venom increases the Poly(I:C)-induced activation in Human Keratinocytes. (2018)
  • Author(s): Nakashima A, Tomono S, Yamazaki T, Morita N, Ichimonji I, Takagi H, Nagaoka H, Matsumoto M, Inui M, Yanagishita T, Watanabe D, Akashi-Takamura S.
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] Plasma level of cis-4-decenal is a possible risk marker for susceptibility to colorectal cancer (2016)
  • Author(s): Tomono, S., Yamaji, T., Iwasaki, M., Narushima, D., Kato, M., Totsuka, Y., Miyoshi, N., Imai, T.
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 新規発がんリスクマーカー探索のための網羅的活性カルボニル化合物解析 (2016)
  • Author(s): 伴野勧、山地太樹、岩崎基、成島大智、加藤護、戸塚ゆ加里、三好規之、大島寛史、今井俊夫
  • Organizer: がん予防学術集会2016名古屋
  • Place of Presentation: 名古屋
  • Year and Date: 2016-07-01