Physiological functions of nuclear lipid droplets

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06733
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Ohsaki Yuki 札幌医科大学, 医学部, 教授 (00378027)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脂肪滴 / 中性脂質 / PML / 核膜変形 / 核内構造体

Outline of Final Research Achievements

Lipid droplets (LD) composed of neutral lipids and phospholipids monolayer can exist not only in the cytoplasm but in the nucleus. We identified different nuclear LD biogenesis mechanisms; one is specific to hepatic cells in which nuclear LDs are derived from lipoprotein precursors in the ER lumen, and another is for general cells in which LDs can be formed by a series of the enzymes of neutral lipid synthesis in the inner nuclear membrane. As functions of nuclear LDs, they were involved in phosphatidylcholine de novo synthesis and ameliorated ER stress in hepatic cells. In glioma cells, nuclear LD-PML complex bodies were related in the transcriptions of several tumor promoting factors. On the other hands, we found that nuclear LDs are frequently formed in human hepatocytes derived from biopsy of patients with various types of hepatic diseases. Further, we also found a family of ER/nuclear membrane proteins that can regulate the amount of nuclear LDs and nuclear membrane invagination.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

半世紀以上謎の構造であった核内脂肪滴の形成機構と複数の生理的意義を明らかにした。特異な疎水性構造であるが、表面にリン脂質一重膜を持つ脂肪滴は、従来の膜を持たない核内構造体（PML小体、核小体など）に新たな機能を付加する可能性があり、新たな創薬標的の基礎研究拡大が期待される。さらに実際の人肝疾患患者で高頻度に核内脂肪滴が形成されており、従来の脂肪肝指標である細胞質脂肪滴蓄積と必ずしも相関しなかったことからも、特定の肝疾患に対して新たな特徴として定義づけられれば、原因不明の肝炎等の鑑別診断、治療の一助となる可能性が高い。