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SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis
Nature Metabolism Pub Date : 2019-11-15 , DOI: 10.1038/s42255-019-0136-6
Zuojun Liu, Minxian Qian, Xiaolong Tang, Wenjing Hu, Shimin Sun, Guo Li, Shuju Zhang, Fanbiao Meng, Xinyue Cao, Jie Sun, Cheng Xu, Bing Tan, Qiuxiang Pang, Bosheng Zhao, Zimei Wang, Youfei Guan, Xiongzhong Ruan, Baohua Liu

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 of Sirt7 in 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.
更新日期:2019-11-17

 

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