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

Baohua Liu

Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China

National Engineering Research Center for Biotechnology (Shenzhen), Carson International Cancer Center, Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China  

November 19, 2019

SIRT7 ensures phase coherence between the central and peripheral clocks and maintains glucose homeostasis.

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.

Nature Metabolism volume 1, pages1141–1156(2019)

DOI:https://doi.org/10.1038/s42255-019-0136-6