Circadian Clock Controlled By The Liver Too

Get up early and align body rhythms with the rising sun. PK Studio/Shutterstock

New research showed that the internal circadian clock is influenced not by the brain only, as previously thought, but by the liver as well.

Collaboration between scientists from the University of Queensland’s Institute for Molecular Bioscience in Australia and Université Paris Cité/CNRS in France has discovered that by transplanting human liver cells in mice, the circadian cycle of mice can be modified.

Associate Professor Frédéric Gachon from UQ’s Institute for Molecular Bioscience told UQ News that when the researchers implanted human cells into the mice, their circadian rhythm changed.

“Mice are nocturnal, but when their liver cells were replaced with human cells, their circadian clock advanced by two hours—hey 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.”

A mouse is seen in a plastic box at the Laboratory Animal Services Center (LASC) of the University of Zurich in Schlieren, Switzerland, on Feb. 7, 2022. Arnd Wiegmann/Reuters

What Is Circadian Clock?

The circadian clock is an internal biological system that regulates various physiological processes in organisms, including humans, animals, plants, and even some microorganisms.

It helps to synchronize these processes with the 24-hour day-night cycle of the Earth.

The word “circadian” comes from the Latin words “circa” (meaning “around”) and “dies” (meaning “day”), which reflects the approximately 24-hour cycle that the circadian clock operates on.

The circadian clock is responsible for regulating sleep-wake cycles, hormone production, body temperature, metabolism, and other physiological functions.

Exposure to light leads to advances or delays in your circadian rhythm, known as phase shifts. Shutterstock

In humans, the master circadian clock is located in a small region of the brain called the suprachiasmatic nucleus (SCN), which is located in the hypothalamus.

The hypothalamus is a small, pea-sized region located at the base of the brain, just above the brainstem, and it is a crucial part of the central nervous system, as it plays a vital role in maintaining homeostasis, regulating various bodily functions, and controlling the release of hormones by interacting with the pituitary gland.

The SCN receives information about light and darkness from the eyes, specifically through specialized cells called ganglion cells that are sensitive to light, which transmit signals to the SCN, which then regulates the release of melatonin. This hormone helps control the sleep-wake cycle.

The circadian clock is not solely influenced by light cues, and it can also be affected by other environmental factors, such as temperature, feeding schedules, social interactions, and even certain medications.

Disruptions to the circadian clock, such as those experienced during shift work or travel across time zones, can lead to a condition known as circadian rhythm sleep disorders, where the sleep-wake cycle becomes misaligned with the desired schedule.

What Is New In This Study?

So far, the understanding of the mammalian circadian rhythm is that it is controlled only by a central circadian clock consisting of the SCN cells, as explained above.

But Gachon said that their study had changed this understanding as the human cells they introduced in the mice’s liver had not only changed mice’s circadian behaviour but it suggests that curing liver dysfunctions could help restore humans’ overall health and wellbeing.

“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 explains.

“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 wellbeing of patients.

“It also shows that the regulation of circadian rhythms is more complex than we suspected and presents avenues for investigating potential new treatments for metabolic diseases.”

The study also suggests that curing liver dysfunctions could help restore the overall health and wellbeing of humans. freepik

As Gachon said, research on the circadian clock has shown its importance in maintaining overall health and wellbeing.

Thus understanding better the circadian clock, including its molecular mechanisms and genetic regulation, will have positive implications for various fields, including sleep medicine, chronobiology, and the development of treatments for sleep disorders and other related health conditions.

This new study was published in Science Advances.