SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis
SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis
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SIRT7 将光驱动的体温线索与肝脏昼夜节律相位一致性和糖异生结合起来
DOI：
10.1038/s42255-019-0136-6
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发表时间：
2019-11-01
影响因子：
20.8
通讯作者：
Liu, Baohua
中科院分区：
文献类型：
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作者：
Liu, Zuojun;Qian, Minxian;Liu, Baohua
下丘脑视交叉上核（SCN）的中枢起搏器与外周振荡器一起协调全身的生理和行为活动。SCN和外周之间的昼夜节律相位相干性是如何控制的还不清楚。在这里，我们将肝脏SIRT 7确定为对光的早期响应元件，以确保小鼠肝脏中的昼夜节律相位一致性。SCN驱动的体温（BT）振荡诱导HSP 70的节律性表达，其促进SIRT 7泛素化和蛋白酶体降解。急性温度挑战抑制BT振荡，并导致肝脏昼夜节律相位提前。此外，肝脏SIRT 7使BMP 1脱乙酰基，促进其FBXL 3介导的降解并调节肝脏时钟和葡萄糖稳态。Sirt 7在小鼠中的缺失导致在白天限制的喂养时提前的肝脏昼夜节律相和肝脏时钟的快速夹带。这些数据确定了一个BT-HSP 70-SIRT 7-CRYST 1轴，该轴将小鼠肝脏时钟与中央起搏器耦合，并确保昼夜节律相位一致性和葡萄糖稳态。
The central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes peripheral oscillators to coordinate physiological and behavioural activities throughout the body. How circadian phase coherence between the SCN and the periphery is controlled is not well understood. Here, we identify hepatic SIRT7 as an early responsive element to light that ensures circadian phase coherence in the mouse liver. The SCN-driven body temperature (BT) oscillation induces rhythmic expression of HSP70, which promotes SIRT7 ubiquitination and proteasomal degradation. Acute temperature challenge dampens the BT oscillation and causes an advanced liver circadian phase. Further, hepatic SIRT7 deacetylates CRY1, promotes its FBXL3-mediated degradation and regulates the hepatic clock and glucose homeostasis. Loss ofSirt7in mice leads to an advanced liver circadian phase and rapid entrainment of the hepatic clock upon daytime-restricted feeding. These data identify a BT–HSP70–SIRT7–CRY1 axis that couples the mouse hepatic clock to the central pacemaker and ensures circadian phase coherence and glucose homeostasis.