Sirt1 regulates sucrose preference

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16139
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: Matsui Sho 群馬大学, 生体調節研究所, 研究員 (80739673)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 糖質嗜好性 / SIRT1 / FGF21 / Oxytocin

Outline of Final Research Achievements

Diet affects health as calorie and macronutrients once ingested. Macronutrient balance of ingested food affects health span, yet the mechanisms that regulate macronutrient-based diet selection are poorly understood. The health-promoting effects of a dietary regimen caloric restriction are partly mediated by SIRT1, which promotes fat utilization in peripheral tissues. We showed that SIRT1-mediated suppression of simple sugar preference required oxytocin signaling, and SIRT1 in oxytocin neurons was sufficient for the effect. The hepatokine FGF21 acted as an endocrine signal of simple sugar ingestion to oxytocin neurons; it promoted neuronal activation and oxytocin transcription, and it suppressed the simple sugar preference. Moreover, SIRT1 promoted FGF21 signaling in oxytocin neurons, and stimulated oxytocin transcription through NRF2. Therefore, neuronal SIRT1 regulate simple sugar preference via FGF21-oxytocin signaling.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

現在の抗肥満のための摂食調節研究は、エネルギー恒常性の観点 (どれだけ食べるのか) からのものが大半であり、食嗜好の観点 (何を食べるのか) からのアプローチが不足している。本研究の特色は、エネルギー恒常性の観点からの摂食調節研究の知見を発展させて、食嗜好の問題に取り組む点にある。また、本研究の成果は、炭水化物過剰摂取により誘発される糖尿病をはじめとする生活習慣病に対する新たな治療法の開発に繋げる可能性を秘めている。