Nuclear in situ metabolisms and nuclear receptors.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K20592
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Tohoku University
• Principal Investigator: Ogura Toshihiko 東北大学, 加齢医学研究所, 教授 (60273851)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: 核内受容体 / リガンド / 核内脂質 / 核内脂質代謝系 / エネルギー代謝

Outline of Final Research Achievements

In this research project, we found and analyzed several factors that rapidly shuttle from cytoplasm into nucleus in response to mechanical stimuli. Interestingly, some of these factors are lipid metabolizing enzymes, suggesting that even in the nucleus, these enzymes constitute unique metabolic systems, by which ligands of nuclear receptors are synthesized in situ to regulate cellular energy metabolism. To uncover the nuclear lipid metabolism, we have identified many nuclear enzymes extensively. In addition, we analyzed nuclear lipids by MASS spectrometry in a semi-comprehensive way and made detailed lists of the cytoplasmic and nuclear lipids, which provide important information and insights on the nuclear lipids and their unique metabolic pathways. Our research opened a new direction and made a novel concept on the nuclear lipids, which has never been described.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

核内受容体のリガンドは，ホルモンとして異なる組織で生成され，血流で運ばれて標的組織の受容体を活性化すると考えられてきた。しかし，基本的に水溶性の低い脂質様リガンドが，このようなステップで動いているのか，多くの疑問があった。今回の研究成果から，核内にも脂質代謝系が存在し，核内受容体リガンドとなる脂質を生成できること，核と細胞質の脂質に大きな違いがあることがわかり，肥満，糖尿病の発症にも関与する核内リガンドの見解に新しい局面を開いた。核内にユニークな脂質代謝系があること自体，大きな発見であり，この学術的意義はきわめて大きく，内在性核内受容体リガンドの研究に大きな一石を投じることとなった。