Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice.
Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice.
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DOI：
10.1038/s41467-018-07033-z
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发表时间：
2018-11-02
影响因子：
16.6
通讯作者：
Kitamura T
中科院分区：
文献类型：
--
作者：
Matsui S;Sasaki T;Kohno D;Yaku K;Inutsuka A;Yokota-Hashimoto H;Kikuchi O;Suga T;Kobayashi M;Yamanaka A;Harada A;Nakagawa T;Onaka T;Kitamura T
饮食通过摄入热量和大量营养素影响健康，而大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知之甚少。先前的研究表明，NAD依赖性去乙酰化酶sirtuin-1（SIRT 1）通过促进外周组织中的脂肪使用，部分影响热量限制的健康促进作用。在这里，我们发现神经元SIRT 1将小鼠的饮食选择从蔗糖转移到脂肪，与外周代谢转移相匹配。SIRT 1介导的对简单糖偏好的抑制需要催产素信号传导，而催产素神经元中的SIRT 1驱动这种效应。肝细胞因子FGF 21作为催产素神经元的内分泌信号，促进神经元活化和Oxt转录，并抑制单糖偏好。SIRT 1促进催产素神经元中的FGF 21信号传导，并通过NRF 2刺激Oxt转录。因此，神经元SIRT 1有助于小鼠基于大量营养素的饮食选择的稳态调节。SIRT 1是一种NAD+依赖性脱乙酰酶，其功能与生物体寿命，衰老和代谢有关。在这里，Matsui及其同事表明，神经元SIRT 1可以影响小鼠营养相关的饮食选择，这种影响是由FGF 21信号和催产素介导的。
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. SIRT1 is a NAD+-dependent deacetylase whose functions have been linked to organismal longevity, aging and metabolism. Here, Matsui and colleagues show that neuronal SIRT1 can affect nutrient-related dietary choice in mice, and this effect is mediated by FGF21 signalling and oxytocin.
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影响因子：
29
作者：
Hall KD;Bemis T;Brychta R;Chen KY;Courville A;Crayner EJ;Goodwin S;Guo J;Howard L;Knuth ND;Miller BV 3rd;Prado CM;Siervo M;Skarulis MC;Walter M;Walter PJ;Yannai L
通讯作者：
Yannai L
影响因子：
4.6
作者：
Inutsuka A;Yamashita A;Chowdhury S;Nakai J;Ohkura M;Taguchi T;Yamanaka A
通讯作者：
Yamanaka A
影响因子：
4.9
作者：
Gallego-Escuredo, J. M.;Gomez-Ambrosi, J.;Villarroya, F.
通讯作者：
Villarroya, F.
影响因子：
2.7
作者：
Billings, Lyndsey B.;Spero, Jonathan A.;Amico, Janet A.
通讯作者：
Amico, Janet A.
影响因子：
10.5
作者：
Chen, Danica;Bruno, Joanne;Guarente, Leonard
通讯作者：
Guarente, Leonard