Angptl8 mediates food-driven resetting of hepatic circadian clock in mice

Siyu Chen, Mengyang Feng, Shiyao Zhang, Zhewen Dong, Yifan Wang, Wenxiang Zhang and Chang Liu ()
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Siyu Chen: China Pharmaceutical University
Mengyang Feng: China Pharmaceutical University
Shiyao Zhang: China Pharmaceutical University
Zhewen Dong: China Pharmaceutical University
Yifan Wang: China Pharmaceutical University
Wenxiang Zhang: China Pharmaceutical University
Chang Liu: China Pharmaceutical University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Diurnal light-dark cycle resets the master clock, while timed food intake is another potent synchronizer of peripheral clocks in mammals. As the largest metabolic organ, the liver sensitively responds to the food signals and secretes hepatokines, leading to the robust regulation of metabolic and clock processes. However, it remains unknown which hepatokine mediates the food-driven resetting of the liver clock independent of the master clock. Here, we identify Angptl8 as a hepatokine that resets diurnal rhythms of hepatic clock and metabolic genes in mice. Mechanistically, the resetting function of Angptl8 is dependent on the signal relay of the membrane receptor PirB, phosphorylation of kinases and transcriptional factors, and consequently transient activation of the central clock gene Per1. Importantly, inhibition of Angptl8 signaling partially blocks food-entrained resetting of liver clock in mice. We have thus identified Angptl8 as a key regulator of the liver clock in response to food.

Date: 2019
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DOI: 10.1038/s41467-019-11513-1

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