Functional roles of FGF23/alpha-Klotho system in the regulation of food intake.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19924
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: Wakayama Medical University
• Principal Investigator: Komori Tadasuke 和歌山県立医科大学, 医学部, 講師 (90433359)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 視床下部 / FGF23 / αKlotho / 摂食調節

Outline of Final Research Achievements

To investigate the functional roles of FGF23 in the hypothalamus, we injected FGF23 intracerebroventricularly into fasted mice. Intracerebroventricular injection of FGF23 induced the expression of Egr1 in the hypothalamus. In addition, amount of 2-hour food intake was increased by FGF23. FGF23 induced the gene expression of NPY and AgRP in the hypothalamus. These results suggest that FGF23 is a novel important regulator of food intake during fasting. Next, we analyzed the body temperature in αKlotho-deficient mice in both fed and fasted conditions. As homozygous αKlotho-deficient mice show severe physical abnormalities like human premature aging, we used heterozygous αKlotho-deficient (αKlotho+/-) mice. There were no differences in the body temperature between WT and αKlotho+/- mice in the fed condition. However, the fasting-induced decrease in body temperature observed in WT mice was less severe in αKlotho+/- mice.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

健康寿命（健康上の問題で日常生活が制限されることなく生活できる期間）延伸の鍵は適切な食事と運動にあると考えられおり、食事や運動が個体の老化に及ぼす影響の分子機序が注目されている。抗老化遺伝子であるαKlothoの発見により様々な個体の老化メカニズムが明らかとなってきたが、FGF23/αKlothoシステムと摂食や運動との関連性は不明のままであった。本研究では、αKlothoとそのリガンドであるFGF23が視床下部において摂食・エネルギー代謝を制御する新たな因子である事を発見した。これらの結果は、中枢神経系を介した個体の老化メカニズムの解明へと繋がることが期待される。