The Circadian rhythm is a natural cycle of physical, mental, and behavioral changes that the body goes through in a 24-hour cycle. Circadian rhythms are mostly affected by light and darkness and are controlled by a small area in the middle of the brain. Now, a new study in mice led by researchers at the University of Queensland (UQ) has revealed liver cells influence the body’s internal circadian clock, which was previously believed to be solely controlled by the brain.
The findings are published in Science Advances in an article titled, “Mice with humanized livers reveal the role of hepatocyte clocks in rhythmic behavior.”
“The synchronization of circadian clock depends on a central pacemaker located in the suprachiasmatic nuclei,” wrote the researchers. “However, the potential feedback of peripheral signals on the central clock remains poorly characterized. To explore whether peripheral organ circadian clocks may affect the central pacemaker, we used a chimeric model in which mouse hepatocytes were replaced by human hepatocytes. Liver humanization led to reprogrammed diurnal gene expression and advanced the phase of the liver circadian clock that extended to muscle and the entire rhythmic physiology. Similar to clock-deficient mice, liver-humanized mice shifted their rhythmic physiology more rapidly to the light phase under day feeding. Our results indicate that hepatocyte clocks can affect the central pacemaker and offer potential perspectives to apprehend pathologies associated with altered circadian physiology.”
Associate professor Frédéric Gachon from UQ’s Institute for Molecular Bioscience, Serge Luquet, PhD, from Université Paris Cité/CNRS in France, and their collaborators have demonstrated that mice with transplanted human liver cells had modified circadian rhythms.
“Mice are nocturnal but when their liver cells were replaced with human cells, their circadian clock advanced by two hours—they ate and slept at different times to mice without those transplanted cells,” Gachon said.
“The mice in our study started to eat and be active before night-time began, which is very unusual for a nocturnal animal. Liver disease and metabolic diseases such as diabetes and obesity are associated with disrupted sleep, irregular eating, and a disturbance of the circadian clock,” Gachon added.
“This study suggests that the abnormal liver function is likely driving this disturbed rhythm. Our study deepens our understanding of the hormonal and neuronal mechanisms involved in the role of the liver in controlling circadian rhythms. It suggests that restoring liver physiology could benefit the health and well-being of patients.”
Their findings demonstrate that the regulation of circadian rhythms is more complex than we suspected and presents the potential for new treatments for metabolic diseases.