A new study by Keck School of Medicine of USC researchers shows a high fat, high cholesterol diet can trigger changes in the immune system that lead to a serious form of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease is one of the most common causes of liver disease in the United States, and an estimated 20 percent of people with NAFLD have non-alcoholic steatohepatitis, which can eventually progress to cirrhosis or liver cancer, especially in those with obesity or Type 2 diabetes, according to the study.
Patients with NAFLD, particularly African Americans, are also at an increased risk of cardiovascular disease.
“Despite its increasing prevalence and burden to the health care system, there are currently no U.S. Food and Drug Administration-approved therapies for non-alcoholic fatty liver disease,” said the study’s corresponding author, Dr. Hugo Rosen, professor and chair of the Department of
Medicine at the Keck School. “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.”
The study, published in Hepatology, illuminates how a toxic combination of dietary fat and cholesterol impacts the behavior 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 non-alcoholic steatohepatitis.
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.
Oxidized low-density lipoprotein cholesterol, in particular, directly altered gene expression in both human and mouse macrophages associated with inflammation and scar formation.
