Tick tock – the liver controls the circadian clock

18 May 2023

Liver cells influence the body’s internal circadian clock, which was previously believed to be solely controlled by the brain, IMB-led research has revealed.

Associate Professor Frédéric Gachon from IMB’s Centre for Cell Biology of Chronic Disease and Dr Serge Luquet from Université Paris Cité/CNRS in France and their collaborators have demonstrated that mice with transplanted human liver cells had modified circadian rhythms.

Dr Gachon said the circadian internal body clock controls most biological functions including sleep, hormone secretion, body temperature and metabolism.

silhouette of person with clock on their body

Change in sleeping and eating times

“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,” Dr 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.”

Until now, the synchronisation of the mammalian circadian rhythm was thought to be controlled exclusively by a central circadian clock composed of a group of brain cells called the suprachiasmatic nucleus.

Clock is disturbed in diabetes and obesity

body with liver shape highlighted
The disruption of the circadian clock is associated with obesity, type 2 diabetes and liver diseases.

Dr Gachon says this study shows human liver cells in a mouse can act on the central clock and modify circadian behaviour.

“Liver disease and metabolic diseases such as diabetes and obesity are associated with disrupted sleep, irregular eating and a disturbance of the circadian clock,” Dr Gachon said.

“This study suggests that the abnormal liver function is likely driving this disturbed rhythm.

 

The role of the liver in new treatments

Frederic Gachon
Associate Professor Frédéric Gachon

“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 research was published in Science Advances.
 

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