David Li, PhD

American Liver Foundation Postdoctoral Research Fellowship Award
$25,000 over one year

University of Pennsylvania

The effects of lipid composition on hepatocyte lipid droplet crystal formation, mechanics, and fibrogenicity
Mentor: Rebecca G. Wells, MD

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease, or NAFLD) is the most common form of liver disease and is associated with over one-third of liver disease-related deaths in the United States. MASLD is characterized by abnormal liver fat storage and the presence of a cardiometabolic risk factor such as high cholesterol, and can lead to liver inflammation and fibrosis, and ultimately to liver failure. How fat storage and high cholesterol combine to cause liver disease progression is not well understood, but my preliminary work shows that a diet high in fat and cholesterol causes the formation of lipid crystals in the liver. In this project, I propose to investigate the formation of lipid crystals in the liver and their role in MASLD progression. I will characterize the changes in liver lipid composition due to high dietary cholesterol and examine the relationship between liver lipid composition and the formation of lipid crystals. I will also determine whether these lipid crystals can stiffen their surroundings and cause cells to generate fibrotic scarring. The identification of a potentially important role for lipid crystals in the MASLD liver may allow us to develop better non-invasive diagnostic tests and to identify new drugs to reduce or reverse the damage caused by MASLD.