Laboratory of Metabolic Signal, Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512, Japan.
Advanced Scientific Research Leaders Development Unit, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512, Japan.
Nat Commun. 2018 Nov 2;9(1):4604. doi: 10.1038/s41467-018-07033-z.
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.
饮食通过摄入的卡路里和宏量营养素影响健康，而宏量营养素平衡影响健康寿命。调节基于宏量营养素的饮食选择的机制尚未完全了解。先前的研究表明，NAD 依赖性脱乙酰酶 SIRT1（Sirtuin-1）通过促进外周组织中的脂肪利用，在一定程度上影响了热量限制的促进健康的作用。在这里，我们表明神经元 SIRT1 使小鼠的饮食选择从蔗糖转向脂肪，与外周代谢转变相匹配。SIRT1 介导的抑制简单糖偏好需要催产素信号，而催产素神经元中的 SIRT1 驱动这种效应。肝源激素 FGF21 作为一种内分泌信号作用于催产素神经元，促进神经元激活和 Oxt 转录，并抑制简单糖偏好。SIRT1 通过 NRF2 促进催产素神经元中的 FGF21 信号传递，并刺激 Oxt 转录。因此，神经元 SIRT1 有助于小鼠基于宏量营养素的饮食选择的体内平衡调节。
