Identification of novel target molecules of beta-Klotho/FGF15 system and their contributions to fetal growth in mice

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21714
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits; Food science
• Research Institution: Foundation for Biomedical Research and Innovation at Kobe
• Principal Investigator: Kobayashi Kanako 公益財団法人神戸医療産業都市推進機構, その他部局等, その他 (10724106)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: β-Klotho / FGF15 / 胎児発育

Outline of Final Research Achievements

β-Klotho/FGF15 system negatively regulates bile acid synthesis via transcriptional control of target molecules in adult mice. β-klotho and Fgf15 are expressed in embryonic stage, but whether they have functional association or not has been unclear. This study showed that β-Klotho expressed in yolk sac is important to receive FGF15 signal from embryo. Moreover, RNA-sequencing analysis revealed genes and metabolic processes regulated by β-Klotho/FGF15 system during embryonic stage in mice.

Free Research Field

栄養学、代謝学

Academic Significance and Societal Importance of the Research Achievements

低出生体重児は成人後に代謝疾患を発症するリスクが高いことが知られているが、胎児の発育を制御するメカニズムには不明な点が多い。本研究では、胎生期においてβ-Klotho/FGF15システムが制御する遺伝子と代謝経路を明らかにした。β-klotho欠損マウス胚とFgf15欠損マウス胚がいずれも発育抑制を呈することから、β-Klotho/FGF15システムの下流にある分子や代謝経路を解析することで胎児の発育制御に関わる新たなメカニズムが明らかになる可能性がある。