Known as non-alcoholic steatohepatitis (NASH), it eventually progresses to cirrhosis or liver cancer, especially in those with obesity or Type 2 diabetes.
Researchers at Keck School of Medicine found how a toxic combination of dietary fat and cholesterol impacts the behaviour of macrophages, a type of white blood cell, in the liver.
The findings of the study are published in the Journal of Hepatology.
Using a mouse model, the study detailed 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.
“Despite its increasing prevalence and burden to the health care system, there are currently no food and drug administration-approved therapies for non-alcoholic fatty liver disease,” said Hugo Rosen, study’s corresponding author.
“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,” he added.
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.