New insight into liver ‘cross-talk’ could help tackle fatty liver disease

Fatty liver disease, linked to obesity, poor diet and alcohol use, is a growing global health concern. Despite its prevalence, effective treatments remain limited.

The international study, with the Centenary Institute as a collaborating partner, reveals how cells lining the liver’s blood vessels send signals that influence how nearby liver cells process and burn fat. When this communication breaks down, fat can accumulate, increasing the risk of liver disease.

The researchers focused on a protein called Heg1, found in liver blood vessel cells. Using preclinical models involving mice, they showed that when Heg1 is lost, the liver becomes much more prone to fat accumulation under stress conditions such as a high-fat diet or alcohol exposure.

Importantly, the team discovered why this happens. Heg1 helps maintain the production of signalling molecules, known as Wnt factors, that tell liver cells to burn fat efficiently. Without these signals, the liver’s fat-burning machinery slows down, leading to fat build-up.

The researchers also found that restoring part of this signalling pathway was able to reverse the problem, reducing fat accumulation in the liver.

Professor Geoff McCaughan, a study co-author from the Centenary Institute’s Centre for Cancer Innovations, said the findings highlight a new level of understanding in liver biology.

“This research shows that liver health isn’t just about what happens inside liver cells themselves, but also about how neighbouring cells communicate with them,” said Professor McCaughan. “Understanding this cross-talk opens up entirely new ways to think about treating fatty liver disease.”

Senior study author Professor Xiangjian Zheng from Tianjin Medical University, and previously a Laboratory Head at the Centenary Institute, said the discovery provides a strong foundation for future therapies and is a continuation of a collaboration that began during his time at Centenary.

“We’ve identified a critical signalling pathway that helps protect the liver from fat accumulation,” said Dr Zheng. “Targeting this pathway could lead to new treatments that restore healthy liver metabolism, particularly in people at risk of fatty liver disease.”

The study was published in the journal Cellular and Molecular Gastroenterology and Hepatology, a highly ranked journal in the field.