Exploration of the mechanism for cellular toxicity by trans fatty acid that is different from natural fatty acids
| Project/Area Number |
19K15775
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | トランス脂肪酸 / インスリン応答性 / Akt / 膜リン脂質 / リン脂質 / インスリンシグナル / リン脂質分子種 / 飽和脂肪酸 |
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| Outline of Research at the Start |
人工のトランス脂肪酸を多く摂取すると、立体構造が類似する天然の飽和脂肪酸を多く摂取した時のように疾患の発症リスクが高まることが報告されている。そこで本研究では、細胞膜でのリン脂質の変化に着目し、人工のトランス脂肪酸が起こす細胞機能の障害に関わる因子を明らかにする。この現象に関わる分子として、すでに特定したAktを中心に、（1）Aktが活性化する場である細胞膜の脂質ラフトのリン脂質に焦点を絞った解析と、（2）リピドミクス解析やマイクロアレイ解析による網羅的な解析を並行して進める。これにより、天然の物質と似た構造の人工の物質が細胞機能を障害し、生体機能を乱すメカニズムの一端が明らかになると考える。
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| Outline of Final Research Achievements |
Excessive intake of industrial produced trans fatty acids (TFAs) induces cellular toxicity. Our previous studies indicate that the mechanism for TFAs-induced cellular toxicity is different from that for saturated fatty acid-induced cellular toxicity. However, detail mechanism for TFAs-induced cellular toxicity is not elucidated. We revealed that persistent exposure to elaidate, a TFA, results in production of elaidate-conjugated phospholipids and alteration in composition of phospholipid species. Moreover, alteration in composition of phospholipid species is involved in an impairment of accumulation of Akt at the plasma membrane. We further found the candidate gene which is involved in elaidate-induced alteration in composition of phospholipid species. Thus, our study indicated a mechanism for TFAs-induced cellular toxicity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、トランス脂肪酸が引き起こす細胞機能障害に関わる分子をいくつか明らかにした。これらの分子の量や活性を指標とすれば、トランス脂肪酸による細胞機能障害の把握や予測が可能になると考える。これによりトランス脂肪酸の摂取量と疾患発症との関係をより正しく評価できる可能性があり、疾患発症との新たな関係の解明や摂取量の提言に貢献できると考える。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Elaidate, a trans fatty acid, suppresses insulin signaling for glucose uptake in a manner distinct from that of stearate2020
Author(s)
Ishibashi, K.,Takeda, Y., Nakata, L., Hakuno, F., Takahashi, SI., Atsumi, G.
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Journal Title
Biochimie
Volume: 117
Pages: 98-107
DOI
Related Report
Peer Reviewed
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[Journal Article] Elevated Expression of Vascular Adhesion Molecule-1, Plasminogen Activator Inhibitor-1, Cyclooxygenase-2, and Thrombomodulin in Human Umbilical Vein Endothelial Cells from Hospitalized Gestational Diabetes Mellitus Patients2019
Author(s)
Takata Y., Nomura K., Ishibashi K., Kido K., Sasamori Y., Hiraike H., Ayabe T., Atsumi G.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 5
Pages: 807-813
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-05-01
Related Report
Peer Reviewed
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