Evaluation a novel molecular mechanism of protecting colon cancer by the foo-derived components

• Project/Area Number: 25750050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Higashimura Yasuki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70628924)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 短鎖脂肪酸 / プロピオン酸 / 大腸 / PPARalpha / MAPキナーゼ / PPARa

Outline of Final Research Achievements

Short chain fatty acids (SCFA) are produced in the colonic lumen mainly by bacterial fermentation of dietary fiber. Emerging evidence shows that SCFA has important physiological and pathophysiological effects on colonic and systemic events. Recently, SCFA is regarded as an effective tool for cancer prevention including colon cancer. However, the effect of SCFA on the physiological functions of colonic epithelial cell is unknown. Results show that propionate, known as a kind of SCFA, induced PPARa expression time-dependently and concentration-dependently in YAMC (a mouse intestinal epithelial cell line) cells. The expression levels of PPARa-responsive genes such as carnitine palmitoyl transferase II (CPTII) and trifunctional protein a (TFPa) were up-regulated in the presence of propionate, thereby suppressing triglyceride (TG) accumulation. Furthermore, propionate-mediated PPARa induction required phosphorylation of extracellular signal-regulated kinase.

Research Products

• [Journal Article] Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice (2016)
  • Author(s): Higashimura Y, Naito Y, Takagi T, Uchiyama K, Mizushima K, Ushiroda C, Ohnogi H, Kudo Y, Yasui M, Inui S, Hisada T, Honda A, Matsuzaki Y, Yoshikawa T
  • Journal Title: Am. J. Physiol. Gastrointest. Liver Physiol. Volume: 310 Issue: 6 Pages: G367-G375
  • DOI: 10.1152/ajpgi.00324.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 寒天由来のオリゴ糖：アガロオリゴ糖の機能性について． (2016)
  • Author(s): 東村泰希・大野木宏・内藤裕二
  • Journal Title: 食品加工技術 Volume: 36(1) Pages: 8-18
  • NAID: 40020748548
• [Journal Article] Immune Efficacy and Safety of Fucoidan Extracted from Gagome Kombu (Kjellmaniella crassifolai) in Healthy Japanese Subjects. (2015)
  • Author(s): Ohnogi H, NaitoY, Higashimura Y, Uno K, Yoshikawa T
  • Journal Title: Japanese Journal of Complementary and Alternative Medicine Volume: 12(2) Pages: 87-93
  • Peer Reviewed
• [Journal Article] Propionate Promotes Fatty Acid Oxidation through the Up-Regulation of Peroxisome Proliferator-Activated Receptor α in Intestinal Epithelial Cells (2015)
  • Author(s): Higashimura, Y., Naito Y., Takagi T., Uchiyama K., Mizushima K., and Yoshikawa T.
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 61 Issue: 6 Pages: 511-515
  • DOI: 10.3177/jnsv.61.511
  • NAID: 130005125490
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The therapeutic potential of zinc sulfate on inflammatory bowel diseases. (2015)
  • Author(s): Higashimura, Y., Naito, Y., Takagi, T., Mizushima, K., and Yoshikawa, T.
  • Journal Title: Ulcer Res. Volume: 42 Pages: 4-4
• [Journal Article] 亜鉛は酸化型／還元型マクロファージの形質分化制御を介して腸管炎症を抑制する． (2015)
  • Author(s): 東村泰希・内藤裕二・髙木智久・内山和彦・水島かつら・吉川敏一
  • Journal Title: G.I. Research Volume: 23(4) Pages: 92-93
• [Journal Article] 非ステロイド性抗炎症薬惹起性小腸潰瘍に対するアガロオリゴ糖の予防効果 (2015)
  • Author(s): 東村泰希・内藤裕二・髙木智久・谷村祐子・水島かつら・春里暁人・福居顕文・寄木浩行・半田修・大野木宏・吉川敏一
  • Journal Title: Vitamins (Japan) Volume: 89 Pages: 53-55
  • Peer Reviewed
• [Journal Article] Beneficial effect of heat-treated Enterococcus faecalis FK-23 on high-fat diet-induced hepatic steatosis in mice. (2014)
  • Author(s): Kondoh, M., Shimada, T., Fukada, K., Morita, M., Katada, K., Higashimura, Y., Mizushima, K., Okamori, M., Naito, Y., and Yoshikawa, T
  • Journal Title: Br. J. Nutr. Volume: 112 Issue: 6 Pages: 868-875
  • DOI: 10.1017/s0007114514001792
  • Peer Reviewed
• [Journal Article] Heme oxygenase-1 and anti-inflammatory M2 macrophages (2014)
  • Author(s): Naito, Y. Takagi, T. Higashimura, Y
  • Journal Title: Arch Biochem Biophys Volume: 564 Pages: 83-86
  • DOI: 10.1016/j.abb.2014.09.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice (2014)
  • Author(s): Higashimura, Y. Naito, Y. Takagi, T. Tanimura, Y. Mizushima, K. Harusato, A. Fukui, A. Yoriki, H. Handa, O. Ohnogi, H. Yoshikawa, T.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 2 Pages: 310-317
  • DOI: 10.1111/jgh.12373
  • NAID: 110009917750
  • Peer Reviewed
• [Journal Article] MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid. (2013)
  • Author(s): Kugai M, Uchiyama K, Tsuji T, Yoriki H, Fukui A, Qin Y, Higashimura Y, Mizushima K, Yoshida N, Katada K, Kamada K, Handa O, Takagi T, Konishi H, Yagi N, Yoshikawa T, Shirasaka Y, Tamai I, Naito Y, and Itoh Y.
  • Journal Title: Cell Physiol Biochem. Volume: 32 Issue: 4 Pages: 942-950
  • DOI: 10.1159/000354497
  • Peer Reviewed
• [Presentation] Agaro-oligosaccharides prevent high-fat diet-induced gut dysbiosis in mice with regard to the correlation between gut microbiota and bile acid profile (2015)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Hiromu Ohnogi, Yoko Kudo, Madoka Yasui, Seina Inui, Jun Mochiduki, Akira Honda, Yasushi Matsuzaki, Toshikazu Yoshikawa
  • Organizer: 6th International Conference on Food Factors (ICoFF2015)
  • Place of Presentation: Seoul
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] 腸内環境の異常“Gut dysbiosis”に対するAgaphytoseの有効性 (2015)
  • Author(s): 東村泰希
  • Organizer: 第2回腸内細菌をターゲットとした食品開発研究会
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-21
  • Invited
• [Presentation] Protective effect of agaro-oligosaccharides on high-fat diet-induced intestinal dysbiosis in mice: correlation between microbiota and bile acid profile (2015)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Katsura Mizushima Hiromu Ohnogi, Yoko Kudo, Madoka Yasui, Seina Inui, Jun Mochiduki, Akira Honda, Yasushi Matsuzaki, Toshikazu Yoshikawa
  • Organizer: Metabolomics2015
  • Place of Presentation: SAN FRANCISCO
  • Year and Date: 2015-06-29
  • Int'l Joint Research
• [Presentation] 亜鉛シグナルを介した酸化型／還元型マクロファージの形質分化制御は腸管炎症の増悪に寄与する (2015)
  • Author(s): 東村泰希、内藤裕二、髙木智久、水島かつら、吉川敏一
  • Organizer: 第68回日本酸化ストレス学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-06-11
• [Presentation] 亜鉛はマクロファージの形質分化制御を介して腸管炎症を抑制する (2015)
  • Author(s): 東村泰希、内藤裕二、髙木智久、水島かつら、吉川敏一
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-05
• [Presentation] Zinc deficiency aggravates intestinal inflammation through the regulation of macrophage polarization (2015)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Toshikazu Yoshikawa
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: yokohama
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] アガロオリゴ糖は腸管バリア機能の調節を介して腸管炎症を抑制する (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、水島かつら、大野木宏、工藤庸子、安井まどか、乾星菜、吉川敏一
  • Organizer: 第１２回日本機能性食品医用学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-13 – 2014-12-14
• [Presentation] ラット抗がん剤誘発脱毛モデルにおけるガゴメ昆布由来フコイダンの保護作用 (2014)
  • Author(s): 東村泰希、内藤裕二、大野木宏、工藤庸子、安井まどか、乾星菜、吉川敏一
  • Organizer: 第１７回日本補完代替医療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-01 – 2014-11-02
• [Presentation] 硫酸亜鉛による炎症性腸疾患治療の可能性 (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、水島かつら、吉川敏一
  • Organizer: 第４２回日本潰瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-31 – 2014-11-01
• [Presentation] 硫酸亜鉛はmetallothionein-1の発現誘導を介して腸管炎症を抑制する (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、辻俊史、水島かつら、吉川敏一
  • Organizer: 第６７回日本酸化ストレス学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 内在性硫化水素はマクロファージの機能調節を介して腸管炎症を抑制する (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、平田育大、水島かつら、吉川敏一
  • Organizer: 第10回HO研究フォーラム
  • Place of Presentation: 京都
  • Year and Date: 2014-08-29
• [Presentation] 亜鉛の腸管炎症制御機構におけるマクロファージの関与 (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、水島かつら、吉川敏一
  • Organizer: 第５１回日本消化器免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] ENDOGENOUS HYDROGEN SULFIDE SUPPRESSES INTESTINAL INFLAMMATION THROUGH THE REGULATION OF MACROPHAGE POLARIZATION (2014)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Ikuhiro Hirata, Katsura Mizushima, Toshikazu Yoshikawa
  • Organizer: Third International Conference on Hydrogen Sulfide in Biology and Medicine
  • Place of Presentation: Kyoto
  • Year and Date: 2014-06-04 – 2014-06-06
• [Presentation] マクロファージの機能調節に起因する硫化水素の腸管炎症抑制作用 (2014)
  • Author(s): 東村泰希、内藤裕二、高木智久、平田育大、水島かつら、吉川敏一
  • Organizer: 第１４回日本NO学会学術集会
  • Place of Presentation: 佐賀
  • Year and Date: 2014-05-16 – 2014-05-17
• [Presentation] Oligosaccharides from agar ameliorate intestinal inflammation through the induction of heme oxygenase-1 expression in macrophages (2014)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Hiromu Ohnogi, Toshikazu Yoshikawa
  • Organizer: The 32nd Annual Meeting of the Japanese Society for Cytoprotection & Cytobiology
  • Place of Presentation: Kyoto
• [Presentation] Zinc sulfate ameliorates murine intestinal inflammation through the induction of metallothionein-1 expression (2014)
  • Author(s): Yasuki Higashimura, Yuji Naito, Tomohisa Takagi, Toshifumi Tsuji, Katsura Mizushima, Toshikazu Yoshikawa
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International
  • Place of Presentation: Kyoto
• [Presentation] 非ステロイド性抗炎症薬惹起性の小腸潰瘍におけるアガロオリゴ糖の予防効果 (2013)
  • Author(s): 東村泰希、内藤裕二、高木智久、水島かつら、谷村祐子、大野木宏、吉川敏一
  • Organizer: 第６６回日本酸化ストレス学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] HO-1高発現M2マクロファージを標的分子にしたIBD治療 (2013)
  • Author(s): 内藤裕二、高木智久、内山和彦、堅田和弘、東村泰希
  • Organizer: 第50回日本消化器免疫学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 硫化水素による腸管炎症制御の可能性 (2013)
  • Author(s): 東村泰希、内藤裕二、高木智久、平田育大、水島かつら、吉川敏一
  • Organizer: 第９回HO研究フォーラム
  • Place of Presentation: 京都
• [Presentation] ヘムオキシゲナーゼ-1の発現誘導を介したアガロオリゴ糖の腸管炎症抑制作用 (2013)
  • Author(s): 大野木宏、内藤裕二、高木智久、東村泰希、水島かつら、吉川敏一
  • Organizer: 第９回HO研究フォーラム
  • Place of Presentation: 京都
• [Presentation] Intestinal inflammation and heme oxygenase-1: role of zinc and macrophages (2013)
  • Author(s): Yuji Naito, Tomohisa Takagi, Yasuki Higashimura
  • Organizer: 第８６回日本生化学会大会
  • Place of Presentation: 横浜
  • Invited
• [Book] Heme Oxygenase-1 Induction Inhibits Intestinal Inflammation. in "Clinical Aspects of Functional Foods and Neutraceuticals" (2014)
  • Author(s): Naito, Y., Takagi, T., Harusato, A., Higashimura, Y., and Yoshikawa, T.
  • Total Pages: 474
  • Publisher: CRC press
• [Remarks] 京都府立医科大学大学院医学研究科消化器内科学教室HP
  • URL: http://www.f.kpu-m.ac.jp/k/syokanai/