Exploration of mechanisms that make differences or similarities in lipotoxicity of saturated and trans fatty acids

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15494
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Teikyo University
• Principal Investigator: Ishibashi Kenichi 帝京大学, 薬学部, 助教 (00707458)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: トランス脂肪酸 / 飽和脂肪酸 / インスリン応答性 / Akt / 膜リン脂質

Outline of Final Research Achievements

Excessive intake of fatty acids induces toxicity in cells, and it is called lipotoxicity. It is reported that intake of saturated fatty acid (SFA) and trans fatty acid (TFA) is involved in an induction of lipotoxicity. However, the mechanism is not elucidated. Our studies indicate that there are distinctive mechanisms for lipotoxicity of SFA and TFA. Therefore, we examined TFA-distinctive mechanism for lipotoxicity using adipocytes persistently exposed to TFA. Our results revealed that impairment of insulin-dependent glucose uptake is caused by suppression of Akt activation in cells persistently exposed to TFA. Moreover, composition of phospholipids in the plasma membrane was altered in the cells. On the other hand, these alterations were not observed in cells persistently exposed to SFA, suggesting that TFA-distinctive lipotoxicity is induced by alteration of composition of phospholipids and suppression of Akt.

Free Research Field

脂質生化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、トランス脂肪酸に特徴的な脂肪毒性に関わる分子を明らかにした。この分子の量や活性を指標とすれば、トランス脂肪酸により脂肪毒性が起こりやすい人なのかを調べられる可能性がある。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がより正しく評価できる可能性があり、WHOの「Trans fat free by 2023」に向けた我が国の政策にも貢献できると考える。