Fatty diet may lead to life-threatening liver disease: Study

High fat and high cholesterol diet may trigger changes in the immune system that can lead to a serious form of non-alcoholic fatty liver disease (NAFLD), a study warns.

An estimated 20 per cent of people with NAFLD have non-alcoholic steatohepatitis (NASH), according to the study published in the journal Hepatology.

NASH can eventually progress to cirrhosis or liver cancer, especially in those with obesity or Type 2 diabetes. Patients with NAFLD are also at an increased risk of cardiovascular disease, they said.

"Despite its increasing prevalence and burden to the health care system, there are currently no US Food and Drug Administration-approved therapies for non-alcoholic fatty liver disease," said Hugo Rosen, a professor at University of Southern California in the US.

 

"There's an urgent need to better understand the causes of non-alcoholic fatty liver disease progression so that successful therapeutics can be designed and brought into clinical practice," Rosen said.

The study illuminates how a toxic combination of dietary fat and cholesterol impacts the behaviour of macrophages, a type of white blood cell, in the liver.

Using a mouse model, the study details the cascade of events in the immune system that eventually leads to the type of liver inflammation and scarring that is commonly seen in patients with NASH.

After feeding mice diets with varying levels of fat and cholesterol, the team found that the combination of both had a synergistically detrimental action on the genes regulating liver inflammation and scarring.

Oxidised low-density lipoprotein cholesterol, in particular, directly altered gene expression in both human and mouse macrophages associated with inflammation and scar formation.

The group also identified a novel type of reparative macrophage that counteracts the inflammation.

"Not only does this study define how fat and cholesterol shape the progression of liver inflammation and scarring, but it also identifies potential pathways that can be targeted for future therapies. That could bring us closer to finding a treatment for a disease that impacts millions of lives around the world," Rosen said.