Elucidation of the molecular mechanisms underlying re-feeding-dependent repression of ileal Fgf15 expression following starvation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22746
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Nihon University
• Principal Investigator: KATAFUCHI Takeshi 日本大学, 医学部, 准教授 (50300976)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: FGF15 / 胆汁酸 / 回腸 / farnesoid X receptor / RNAシークエンス / 摂食 / 絶食

Outline of Final Research Achievements

In this study I hypothesized that a transcription factor is involved in the postprandial reduction of ileal FGF15 expression level after 14 day food entrainment, and performed RNA sequencing using the mouse ileal RNAs under starvation and 3h-post feeding. I then identified 21 transcription factors changing the expression levels 3h after the feeding. Furthermore, I observed no proportional change in the postprandial reduction of ileal FGF15 expression level even by feeding a meal containing cholic acid, suggesting that the involvement of muricholic acid, a natural FXR antagonist in the bile, in the reduction is unlikely. I also found that 1-day food entrainment is enough to observe the reduction of FGF15 level.

Free Research Field

生化学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

FXRアゴニストは非アルコール性肝炎等の疾患の治療薬としての期待が高まっているが、FGF15/19の発現量は主として核内受容体FXRにより調節されるため、そこにはFGF15/19を介した薬効が含まれていると考えられる。本研究は摂食とFGF15/19の発現の関係が明らかにしつつある。従って本研究は食後どのタイミングにおいて投薬をするのが治療効果を最大にするのか、などのFXRアゴニストの薬剤開発における有用な情報を提供できるため、その成果は社会的意義を持つ。