SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis.

Nature Metabolism
Zuojun LiuBaohua Liu

Abstract

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.

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Citations

Nov 4, 2020·EMBO Reports·Alexander NeumannMarco Preußner
Jan 16, 2021·Free Radical Biology & Medicine·Tomoki Sato, Carolina Magdalen Greco
Mar 9, 2021·Cellular and Molecular Life Sciences : CMLS·Leonardo Vinícius Monteiro de Assis, Henrik Oster
Jun 16, 2021·Open Biology·Ming TangWei-Guo Zhu

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Methods Mentioned

BETA
ubiquitination
co-immunoprecipitation
co-IP
immunoprecipitation
pull-down
acetylation
PCR
transgenic
in vitro transcription
Myc-ubiquitination

Software Mentioned

GraphPad
GraphPad Prism
Mascot

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