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Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice

Author

Listed:
  • Sho Matsui

    (Gunma University)

  • Tsutomu Sasaki

    (Gunma University)

  • Daisuke Kohno

    (Gunma University
    Gunma University)

  • Keisuke Yaku

    (University of Toyama
    University of Toyama)

  • Ayumu Inutsuka

    (Nagoya University
    Jichi Medical University)

  • Hiromi Yokota-Hashimoto

    (Gunma University)

  • Osamu Kikuchi

    (Gunma University)

  • Takayoshi Suga

    (Gunma University)

  • Masaki Kobayashi

    (Gunma University)

  • Akihiro Yamanaka

    (Nagoya University)

  • Akihiro Harada

    (Osaka University)

  • Takashi Nakagawa

    (University of Toyama
    University of Toyama)

  • Tatsushi Onaka

    (Jichi Medical University)

  • Tadahiro Kitamura

    (Gunma University)

Abstract

Diet affects health through ingested calories and macronutrients, and macronutrient balance affects health span. The mechanisms regulating macronutrient-based diet choices are poorly understood. Previous studies had shown that NAD-dependent deacetylase sirtuin-1 (SIRT1) in part influences the health-promoting effects of caloric restriction by boosting fat use in peripheral tissues. Here, we show that neuronal SIRT1 shifts diet choice from sucrose to fat in mice, matching the peripheral metabolic shift. SIRT1-mediated suppression of simple sugar preference requires oxytocin signalling, and SIRT1 in oxytocin neurons drives this effect. The hepatokine FGF21 acts as an endocrine signal to oxytocin neurons, promoting neuronal activation and Oxt transcription and suppressing the simple sugar preference. SIRT1 promotes FGF21 signalling in oxytocin neurons and stimulates Oxt transcription through NRF2. Thus, neuronal SIRT1 contributes to the homeostatic regulation of macronutrient-based diet selection in mice.

Suggested Citation

  • Sho Matsui & Tsutomu Sasaki & Daisuke Kohno & Keisuke Yaku & Ayumu Inutsuka & Hiromi Yokota-Hashimoto & Osamu Kikuchi & Takayoshi Suga & Masaki Kobayashi & Akihiro Yamanaka & Akihiro Harada & Takashi , 2018. "Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07033-z
    DOI: 10.1038/s41467-018-07033-z
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