Disrupting the circadian clock protects the liver

22 February 2022

The livers of men diagnosed with hepatic diseases change sex as part of a potential self-protective mechanism, according to Institute for Molecular Bioscience research.

Lead researcher Associate Professor Frederic Gachon said the surprise discovery was made during an investigation into why disruption of the circadian clock is associated with obesity, type 2 diabetes and liver diseases.

'Feminised' livers were free of liver disease

Associate Professor Fred Gachon

“When a high-fat diet was fed to mice that had their circadian clock gene turned off, we expected them to develop diabetes or non-alcoholic fatty liver disease (NAFLD) like the control mice, but they didn’t,” Dr Gachon said.

“We also found that the liver of the obese male mice had been feminised and were free of metabolic and liver disease, probably due in part to the protective nature of the female sex hormone, oestrogen.”

Like reproductive organs, the liver is sexually dimorphic, which means there are significant differences between the metabolic function of male and female livers.

The team then went on to study human samples and got the same results.

Disruption of circadian rhythms protecting the liver

“The more advanced the disease, the more feminisation we saw in the liver tissue,” Dr Gachon said.

“It appears that the disruption of circadian rhythms might be protecting the liver by influencing the levels of hormones such as growth hormone, oestrogen and testosterone.”

The internal body clock controls many biological functions including sleep, hormone secretion, body temperature and metabolism.

A liver disease affecting 25 per cent of adults

Liver in male body
Non-alcoholic fatty liver disease is more prevalent in men.

NAFLD is far more prevalent in men and affects 25 per cent of the adult population, while sleep disorders are a known symptom of the disease.

“This study suggests that the disruption of the circadian clock gives the body flexibility in metabolic pathways that can help to slow down disease progression,” Dr Gachon said.

“In light of these findings, we are investigating whether behavioural and hormonal interventions are possible treatments for liver disease.”

This research was published in PNAS.