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New research shows how a fatty diet can lead to life-threatening liver disease

A study by scientists at the Keck School of Medicine of USC provides new insight on how dietary fat and cholesterol drive the development of non-alcoholic steatohepatitis (NASH), a serious form of non-alcoholic fatty liver disease

University of Southern California - Health Sciences

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IMAGE: This is Hugo Rosen, M.D., professor and chair of the Department of Medicine, Keck School of Medicine of USC. view more 

Credit: Ricardo Carrasco III

LOS ANGELES - A new study by Keck School of Medicine of USC researchers shows there's yet another reason to avoid a high fat, high cholesterol diet: It can trigger changes in the immune system that lead to a serious form of non-alcoholic fatty liver disease (NAFLD) known as non-alcoholic steatohepatitis (NASH).

NAFLD is one of the most common causes of liver disease in the United States, and an estimated 20 percent of people with NAFLD have NASH. 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.

"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," says the study's corresponding author, Hugo Rosen, MD, 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 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. Oxidized 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," he says. "Here at the Keck School, we are committed to building a cutting-edge research and clinical program that identifies mechanisms of NASH, non-invasive approaches for diagnosis and risk stratification, and clinical implementation of novel strategies for treatment."

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About the Keck School of Medicine of USC

Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education and community service. The school has more than 1,750 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 800 medical students and 1,000 students pursuing graduate and postgraduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Keck School faculty also conduct research and teach at several research centers and institutes, including the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, USC CardioVascular Thoracic Institute, USC Institute of Urology, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, USC Norris Comprehensive Cancer Center, USC Roski Eye Institute and Zilkha Neurogenetic Institute.

In 2018, U.S. News & World Report ranked the Keck School among the top 35 medical schools in the country.

For more information, go to keck.usc.edu.

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