Liu, Z;
Qian, M;
Tang, X;
Hu, W;
Sun, S;
Li, G;
Zhang, S;
... Liu, B; + view all
(2019)
SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis.
Nature Metabolism
, 1
(11)
pp. 1141-1156.
10.1038/s42255-019-0136-6.
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SIRT7 circadian manuscript_20190921.pdf - Accepted Version Download (5MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42255-019-0136-6 |
| Publisher version: | http://dx.doi.org/10.1038/s42255-019-0136-6 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10090255 |
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