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2021 Fiscal Year Annual Research Report

Basic and applied research of long-chained unsaturated fatty acid for preventing anti- arteriosclerosis

Research Project

Project/Area Number 19H04055
Research InstitutionThe University of Tokushima

Principal Investigator

阪上 浩  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60372645)

Co-Investigator(Kenkyū-buntansha) 黒田 雅士  徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (00803579)
堤 理恵  徳島大学, 大学院医歯薬学研究部(医学域), 講師 (80510172)
Project Period (FY) 2019-04-01 – 2022-03-31
Keywords一価不飽和脂肪酸 / 動脈硬化 / 魚油 / 二重盲検試験 / トリメチルアミン-N-オキシド / グルカゴン様ペプチド-1
Outline of Annual Research Achievements

研究代表者は、EPAやDHAとは異なるコレステロール低下作用などの代謝改善作用や動脈硬化を予防する作用を有する極長鎖一価不飽和脂肪酸を魚油から分離した。生活習慣病とその重症化予防に対する革新的な技術開発を目的に、その作用機序を解明するとともに標的分子を明らかとし、動脈硬化症への有効性の検証と分析法を確立するため、本年度は(1)から(3)の研究の課題に課題に取り組み、研究成果は以下の通りである。
(1)極長鎖一価不飽和脂肪酸の抗動脈硬化作用機序の解明:2020年度までに明らかとした成果(極長鎖一価不飽和脂肪酸の標的分子として腸内細菌関連代謝物であるトリメチルアミン-N-オキシドの同定、腸内細菌叢の変化により短鎖脂肪酸の産生によるグルカゴン様ペプチド-1の分泌を惹起、腸内細菌-肝臓代謝の観点から動脈硬化モデル動物とヒト検体検討)を踏まえ、本年度には新たに研究代表者がEPAなどの既存脂肪酸に対する極長鎖一価不飽和脂肪酸の上乗せ効果を見出した。
(2)極長鎖一価不飽和脂肪酸の血管内皮機能に対する有効性確認試験の実施:極長鎖一価不飽和脂肪酸の健常成人に対する有効性と、試験により得られたサンプル分析を行い、投与脂肪酸の代謝産物の分析から適切な有効性を示す投与量を決定したことから、本年度は境界域にある健常成人に対して第Ⅱ・Ⅲ相試験を実施し、その有効性を二重盲検試験で明らかとした。
(3)極長鎖一価不飽和脂肪酸分析の実施とヒト健常者の基準値調査:有効成分である一価不飽和長鎖脂肪酸の各種動物実験や臨床試験のサンプルの脂肪酸分析を質量分析にて実施し、一価不飽和長の異性体分析など、その技術的成果を高めた。一価不飽和長鎖脂肪酸分析を徳島県内陸の山間部と海岸部の健常ヒトサンプルでの基準値の調査は、COVID-19の影響で延期された。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

  • Research Products

    (24 results)

All 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Int'l Joint Research] National Institutes of Health(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      National Institutes of Health
  • [Journal Article] Necessity of daily 1000-IU vitamin D supplementation for maintaining a sufficient vitamin D status2022

    • Author(s)
      Ikezumi Yuya、Matsuura Yasushi、Morishita Teruhiro、Ide Noriko、Kitada Isao、Katayama Takafumi、Tsutsumi Rie、Sakaue Hiroshi、Taketani Yutaka、Sairyo Koichi、Takeda Eiji
    • Journal Title

      The Journal of Medical Investigation

      Volume: 69 Pages: 135~140

    • DOI

      10.2152/jmi.69.135

    • Peer Reviewed
  • [Journal Article] Taste receptor gene expression is associated with decreased eGFR in patients with diabetes2022

    • Author(s)
      Beppu Kana、Kawakami Ayuka、Mishima Yuna、Tsutsumi Rie、Kuroda Masashi、Mori Hiroyasu、Kuroda Akio、Matsuhisa Munehisa、Sakaue Hiroshi
    • Journal Title

      The Journal of Medical Investigation

      Volume: 69 Pages: 120~126

    • DOI

      10.2152/jmi.69.120

    • Peer Reviewed
  • [Journal Article] Development of a screening system for agents that modulate taste receptor expression with the CRISPR-Cas9 system in medaka2022

    • Author(s)
      Beppu Kana、Tsutsumi Rie、Ansai Satoshi、Ochiai Nana、Terakawa Mai、Mori Marie、Kuroda Masashi、Horikawa Kazuki、Tomoi Takumi、Sakamoto Joe、Kamei Yasuhiro、Naruse Kiyoshi、Sakaue Hiroshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 601 Pages: 65~72

    • DOI

      10.1016/j.bbrc.2022.02.082

    • Peer Reviewed
  • [Journal Article] TGF‐β‐activated kinase‐1 inhibitor LL‐Z1640‐2 reduces joint inflammation and bone destruction in mouse models of rheumatoid arthritis by inhibiting NLRP3 inflammasome, TACE, TNF‐α and RANKL expression2022

    • Author(s)
      Tenshin Hirofumi、Teramachi Jumpei、Ashtar Mohannad、Hiasa Masahiro、Inoue Yusuke、Oda Asuka、Tanimoto Kotaro、Shimizu So、Higa Yoshiki、Harada Takeshi、Oura Masahiro、Sogabe Kimiko、Hara Tomoyo、Sumitani Ryohei、Maruhashi Tomoko、Sebe Mayu、Tsutsumi Rie、Sakaue Hiroshi、Abe Masahiro
    • Journal Title

      Clinical & Translational Immunology

      Volume: 11 Pages: e1371

    • DOI

      10.1002/cti2.1371

    • Peer Reviewed
  • [Journal Article] Saturated fatty acids intake is associated with muscle atrophy in rheumatoid arthritis2021

    • Author(s)
      Sebe Mayu、Tsutsumi Rie、Senoura Satoka、Kishi Jun、Iuchi Marina、Mishima Yuna、Tsutsumi Yasuo M.、Kuroda Masashi、Harada Nagakatsu、Nakaya Yutaka、Kinoshita Seizo、Nishioka Yasuhiko、Sakaue Hiroshi
    • Journal Title

      JCSM Rapid Communications

      Volume: 5 Pages: 86~101

    • DOI

      10.1002/rco2.53

    • Peer Reviewed
  • [Journal Article] Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora2021

    • Author(s)
      Tsutsumi Rie、Yamasaki Yuki、Takeo Jiro、Miyahara Hiroko、Sebe Mayu、Bando Masahiro、Tanba Yousuke、Mishima Yuna、Takeji Kana、Ueshima Nanako、Kuroda Masashi、Masumoto Saeko、Harada Nagakatsu、Fukuda Daiju、Yoshimoto Ryoko、Tsutsumi Yasuo M、Aihara Ken-ichi、Sata Masataka、Sakaue Hiroshi
    • Journal Title

      Translational Research

      Volume: 237 Pages: 16~30

    • DOI

      10.1016/j.trsl.2021.03.016

    • Peer Reviewed
  • [Journal Article] Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity2021

    • Author(s)
      Miyake Masato、Zhang Jun、Yasue Akihiro、Hisanaga Satoshi、Tsugawa Kazue、Sakaue Hiroshi、Oyadomari Miho、Kiyonari Hiroshi、Oyadomari Seiichi
    • Journal Title

      iScience

      Volume: 24 Pages: 103448~103448

    • DOI

      10.1016/j.isci.2021.103448

    • Peer Reviewed
  • [Journal Article] Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model2021

    • Author(s)
      Morio Atsushi、Tsutsumi Rie、Satomi Shiho、Kondo Takashi、Miyoshi Hirotsugu、Kato Takahiro、Kuroda Masashi、Kitamura Tadahiro、Hara Kenta、Saeki Noboru、Sakaue Hiroshi、Tsutsumi Yasuo M.
    • Journal Title

      Diabetology & Metabolic Syndrome

      Volume: 13 Pages: 139~139

    • DOI

      10.1186/s13098-021-00755-z

    • Peer Reviewed
  • [Journal Article] Dietary supplementation with monosodium glutamate with dietary balance such as protein, salt and sugar intake with increasing T1R3 taste receptor gene expression in healthy females2021

    • Author(s)
      Beppu Kana、Shono Hitoshi、Kawakami Ayuka、Takashi Tomoe、Watanabe Suzuno、Yoshida Akari、Kuroda Masashi、Fujimoto Chisa、Kanamura Ryo、Ohnishi Hiroki、Kondo Eiji、Azuma Takahito、Sato Go、Kitamura Yoshiaki、Tsutsumi Rie、Sakaue Hiroshi、Takeda Noriaki
    • Journal Title

      The Journal of Medical Investigation

      Volume: 68 Pages: 315~320

    • DOI

      10.2152/jmi.68.315

    • Peer Reviewed
  • [Journal Article] Effects of daily 1,000-IU vitamin D-fortified milk intake on skeletal muscle mass, power, physical function and nutrition status in Japanese2021

    • Author(s)
      Matsuura Yasushi、Morishita Teruhiro、Sato Michiko、Sumida Nami、Katayama Takafumi、Tsutsumi Rie、Sakaue Hiroshi、Taketani Yutaka、Sairyo Koichi、Kawaura Akihiko、Takeda Eiji
    • Journal Title

      The Journal of Medical Investigation

      Volume: 68 Pages: 249~255

    • DOI

      10.2152/jmi.68.249

    • Peer Reviewed
  • [Journal Article] Dietary Supplementation with Monosodium Glutamate Suppresses Chemotherapy-Induced Downregulation of the T1R3 Taste Receptor Subunit in Head and Neck Cancer Patients2021

    • Author(s)
      Shono Hitoshi、Tsutsumi Rie、Beppu Kana、Matsushima Rina、Watanabe Suzuno、Fujimoto Chisa、Kanamura Ryo、Ohnishi Hiroki、Kondo Eiji、Azuma Takahiro、Sato Go、Kawai Misako、Matsumoto Hideki、Kitamura Yoshiaki、Sakaue Hiroshi、Takeda Noriaki
    • Journal Title

      Nutrients

      Volume: 13 Pages: 2921~2921

    • DOI

      10.3390/nu13092921

    • Peer Reviewed
  • [Journal Article] Sudachi peel extract powder including the polymethoxylated flavone sudachitin improves visceral fat content in individuals at risk for developing diabetes2021

    • Author(s)
      Shikishima Yasuhiro、Tsutsumi Rie、Kawakami Ayuka、Miura Hiroyuki、Nii Yoshitaka、Sakaue Hiroshi
    • Journal Title

      Food Science & Nutrition

      Volume: 9 Pages: 4076~4084

    • DOI

      10.1002/fsn3.2339

    • Peer Reviewed
  • [Journal Article] Leucine induces cardioprotection in?vitro by promoting mitochondrial function via mTOR and Opa-1 signaling2021

    • Author(s)
      Morio Atsushi、Tsutsumi Rie、Kondo Takashi、Miyoshi Hirotsugu、Kato Takahiro、Narasaki Soshi、Satomi Shiho、Nakaya Erika、Kuroda Masashi、Sakaue Hiroshi、Kitamura Tadahiro、Tsutsumi Yasuo M.
    • Journal Title

      Nutrition, Metabolism and Cardiovascular Diseases

      Volume: 31 Pages: 2979~2986

    • DOI

      10.1016/j.numecd.2021.06.025

    • Peer Reviewed
  • [Journal Article] Assessment of catabolic state in infants with the use of urinary titin N-fragment2021

    • Author(s)
      Fukushima Sachiyo、Nakanishi Nobuto、Fujioka Kazumichi、Suga Kenichi、Shirakawa Taku、Osawa Kayo、Hara Kanako、Tsutsumi Rie、Urushihara Maki、Nakagawa Ryuji、Awano Hiroyuki、Oto Jun、Sakaue Hiroshi、Iijima Kazumoto、Matsuo Masafumi
    • Journal Title

      Pediatric Research

      Volume: 17 Pages: 1~6

    • DOI

      10.1038/s41390-021-01658-5

    • Peer Reviewed
  • [Journal Article] Rectus Femoris Mimicking Ultrasound Phantom for Muscle Mass Assessment: Design, Research, and Training Application2021

    • Author(s)
      Nakanishi Nobuto、Inoue Shigeaki、Tsutsumi Rie、Akimoto Yusuke、Ono Yuko、Kotani Joji、Sakaue Hiroshi、Oto Jun
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Pages: 2721~2721

    • DOI

      10.3390/jcm10122721

    • Peer Reviewed
  • [Journal Article] Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome2021

    • Author(s)
      Nakanishi Nobuto、Tsutsumi Rie、Hara Kanako、Matsuo Masafumi、Sakaue Hiroshi、Oto Jun
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Pages: 614~614

    • DOI

      10.3390/jcm10040614

    • Peer Reviewed
  • [Journal Article] Elevated Urinary Titin and its Associated Clinical Outcomes after Acute Stroke2021

    • Author(s)
      Ishihara Manabu、Nakanishi Nobuto、Tsutsumi Rie、Hara Kanako、Machida Kyoka、Yamamoto Nobuaki、Kanematsu Yasuhisa、Sakaue Hiroshi、Oto Jun、Takagi Yasushi
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 30 Pages: 105561~105561

    • DOI

      10.1016/j.jstrokecerebrovasdis.2020.105561

    • Peer Reviewed
  • [Presentation] 飽和脂肪酸の過剰摂取は疾患性サルコペニア発症のリスクとなる2022

    • Author(s)
      堤 理恵, 阪上 浩
    • Organizer
      第42回日本肥満学会
  • [Presentation] Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora2021

    • Author(s)
      Rie Tsutsumi, Hiroshi Sakaue
    • Organizer
      The 19th International Symposium on Atherosclerosis
    • Int'l Joint Research
  • [Presentation] 極長鎖一価不飽和脂肪酸は腸内細菌叢の変化を介して血管内皮機能を改善2021

    • Author(s)
      米田 祥広, 阪上 浩
    • Organizer
      第 54 回 日本栄養食糧学会 中国四国支部大会
  • [Presentation] 極長鎖一価不飽和脂肪酸は腸内細菌叢の変化を介して血管内皮機能を改善する2021

    • Author(s)
      米田 祥広, 阪上 浩
    • Organizer
      第263回徳島医学会
  • [Presentation] 関節リウマチ患者におけるサルコペニア有病率と体組成評価の有用性2021

    • Author(s)
      瀬部 真由, 阪上 浩
    • Organizer
      第13回日本臨床栄養代謝学会中国四国支部学術集会
  • [Remarks] 徳島大学大学院 医歯薬学研究部 代謝栄養学分野ホームページ/Graphical abstract

    • URL

      https://taishaeiyo.jimdofree.com/graphical-abstracts/

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Published: 2022-12-28  

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