Elucidation of the brain mechanisms of sugar preference by SIRT1

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kyoto University
• Principal Investigator: Matsui Sho 京都大学, 農学研究科, 助教 (80739673)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Oxytocin / FGF21 / 糖

Outline of Final Research Achievements

Oxytocin (Oxt) neurons are mainly located in two places within the brain, the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus of the hypothalamus (SON). Therefore, we asked which Oxt neurons are responsible for regulating simple sugar preference and the effect of SIRT1 on diet selection in mice.
Intraperitoneal injection of the recombinant murine FGF21 to mice induced c-Fos in approximately 13 % of PVH Oxt, but no significant activation was detected in SON Oxt neurons. Therefore, PVH Oxt neurons are one of the target of FGF21 in the hypothalamus.
We next manipulated the SIRT1 expression levels in PVH vs. SON Oxt neurons by injecting Cre-inducible SIRT1 (WT or enzyme-dead H355Y mutant) AAV vector to Oxt-ires Cre mice. The overexpression of SIRT1-WT in PVH Oxt neurons significantly suppressed simple sugar preference, but no significant effect was observed in the SON-injected group. Therefore, SIRT1 suppresses simple sugar preference through PVH Oxt neurons in mice.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

糖質は食行動の引き金として強力に作用し、必要以上のエネルギー摂取をもたらすことで、肥満発症の要因になる。肥満症に用いられる治療薬は、中枢・末梢神経系や心臓に対する重篤な副作用が多く認められる。本研究の成果から、オキシトシンニューロンのタイプや投射先の脳領域を特定することができれば、糖質嗜好性が原因となる肥満症に対して、より特異性が高く副作用の少ない抗肥満薬の開発につながることが期待される。