Development of prevention and treatment strategies for trans-fatty acid-related diseases based on novel toxicity mechanisms

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14894
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tohoku University
• Principal Investigator: Hirata Yusuke 東北大学, 薬学研究科, 助教 (10748221)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: トランス脂肪酸 / DNA損傷 / 細胞死 / 老化 / 脂肪肝

Outline of Final Research Achievements

We found that trans-fatty acids (TFAs) promote DNA damage-induced cell death by increasing mitochondrial reactive oxygen species (ROS) generation in a manner dependent on JNK, a stress-responsive MAP kinase.
A toxicological evaluation revealed that industrial TFAs, produced during food manufacturing processes, possess much higher toxicity than ruminant TFAs, produced by microbes in ruminant stomach.
An in vivo experiment demonstrated that the livers of mice fed with TFA-containing high fat diet showed more fat accumulation and accelerated senescence/inflammation than those fed with normal high fat diet, implicating that the pro-senescence/inflammation functions of TFAs link with fatty liver diseases.

Free Research Field

ストレス応答

Academic Significance and Societal Importance of the Research Achievements

トランス脂肪酸は、これまで主に疫学調査研究から動脈硬化症等の諸疾患との関連が示されてきた一方で、分子レベルでの作用機構については解明が進んでおらず、詳細な病態発症機序は不明であった。本研究成果により、トランス脂肪酸の病態発症機序解明に繋がる新たな毒性発現機構が解明されると共に、特に病態発症との関連が示唆されてきた人工型トランス脂肪酸の方が、天然型よりも強力な毒性を有することが明らかとなり、過去の疫学研究の科学的な裏付けができた。