Angptl8 shortened the circadian period to 23.68 hours compared to 23.92 hours with vehicle and advanced the phase of activity rhythms by 1.67 hours in mice.
Does Angptl8 mediate food-driven resetting of the hepatic circadian clock in mice?
Angptl8 acts as a key hepatokine that mediates food-driven resetting of the liver circadian clock independent of the central master clock.
Absolute Event Rate: 23.68% vs 23.92%
p-value: p=0.004
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.
Chen et al. (Tue,) conducted a other in Circadian clock resetting. Angptl8 vs. PBS (vehicle) was evaluated on Circadian period (hours) (p=0.004). Angptl8 shortened the circadian period to 23.68 hours compared to 23.92 hours with vehicle and advanced the phase of activity rhythms by 1.67 hours in mice.