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

Sho Matsui, Tsutomu Sasaki (), Daisuke Kohno, Keisuke Yaku, Ayumu Inutsuka, Hiromi Yokota-Hashimoto, Osamu Kikuchi, Takayoshi Suga, Masaki Kobayashi, Akihiro Yamanaka, Akihiro Harada, Takashi Nakagawa, Tatsushi Onaka and Tadahiro Kitamura ()
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Sho Matsui: Gunma University
Tsutomu Sasaki: Gunma University
Daisuke Kohno: Gunma University
Keisuke Yaku: University of Toyama
Ayumu Inutsuka: Nagoya 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
Tatsushi Onaka: Jichi Medical University
Tadahiro Kitamura: Gunma University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07033-z

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