Exploration for Polyunsaturated Fatty Acids (PUFA)-responsive domain on Sterol Regulatory Element-binding Protein-1

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K12895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: The University of Tokyo
• Principal Investigator: Masuda Yukari 東京大学, 医学部附属病院, 特任助教 (50768554)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脂質代謝異常 / 動脈硬化性疾患 / ニュートリゲノミクス / 多価不飽和脂肪酸（PUFA） / SREBP

Outline of Final Research Achievements

Polyunsaturated fatty acids (PUFA), representedby fish oil, are a therapeutic agent for dyslipidemia which suppresses triglyceride synthesis in the liver. PUFA have various beneficial physiological effects, but their metabolic pathway is still unclear. In previous study, we successfully established an assay system to analyze the activities of proteolytic processing of SREBP (sterol regulatory element-binding protein; a key transcription factor for the regulation of lipogenic enzyme genes) in the liver of living mice by using in vivo imaging system (IVIS), and clarified the molecular mechanisms by which PUFA selectively suppress SREBP-1, but not SREBP-2, which is similar in sequence. In this study, we tried to explore the PUFA-responsive domain on SREBP-1 and to search for interacting new molecules.

Free Research Field

代謝学　栄養学

Academic Significance and Societal Importance of the Research Achievements

PUFAは体内で合成が出来ず、食事に頼るべき必須脂肪酸であるが、本邦では食生活の欧米化等に伴い魚油（PUFA）の摂取量が年々減少し、動脈硬化性疾患（虚血性心疾患や脳卒中）による寝たきり率や死亡率が増加している。PUFAの摂取不足は、他にも様々な病態や疾患を引き起こす事が知られているにも関わらず、代謝動態に未知な点が多い。本研究は、脂質代謝を制御する重要な転写因子SREBPとPUFAの関連をニュートリゲノミクスの観点から追究した。本研究の発展は、脂質代謝が関与する様々な病態の解明の一端を担うことで、多くの人々の健康寿命の延長に繋がる。