Elucidating how the longevity gene SIRT1 regulate alcohol preference.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19726
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Kyoto University (2019); Gunma University (2018)
• Principal Investigator: Sasaki Tsutomu 京都大学, 農学研究科, 教授 (50466687)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 飲酒 / FGF21 / オキシトシン / 嗜好性 / SIRT1

Outline of Final Research Achievements

Alcohol dependence is a major health burden, but the treatment options are limited. Therefore, we aimed to elucidate the molecular and neural basis that regulates alcohol preference, focusing on FGF21, oxytocin, and SIRT1.
We found that overexpression of SIRT1 specifically in the nervous system or in the oxytocin neurons significantly suppressed alcohol preference in mice. However, deleting SIRT1 specifically in the nervous system or in the oxytocin neurons did not affect alcohol preference in mice.
Feeding mice a SIRT1 activator resveratrol for 2 weeks significantly suppressed alcohol preference in the wild-type mice. However, supplementing a precursor of NAD+, a co-factor for SIRT1 activity, nicotinamide mononucleotide (NMN) for 2 weeks did not affect alcohol preference in the wild-type mice.

Free Research Field

神経科学、内分泌代謝学、食品科学、栄養学

Academic Significance and Societal Importance of the Research Achievements

アルコール嗜好性を制御する新たな分子・神経基盤を解明し、特許出願を行った。SIRT1の活性化剤の長期投与により、アルコール嗜好性を抑制できる可能性は示すことが出来たが、同様の作用機序が推察される前駆体補充療法では有意な効果が得られなかったため、SIRT1を分子標的にしてアルコール嗜好性を抑制することは、現実的には難しいのではないかとの結論に至った。