Lipotoxicity and Liver Inflammation

PROJECT NARRATIVE The proposal examines the mechanisms of liver injury and inflammation in nonalcoholic fatty liver disease by employing models related to obesity. We propose that liver cells exposed to excess circulating toxic lipids such as saturated free fatty acids and their metabolites release abundant extracellular vesicles, which induce recruitment and retention of white blood cells into the liver and promote liver inflammation. The results of the proposal have the potential to identify new mechanisms of liver inflammation in nonalcoholic fatty liver disease (the most common pediatric liver disease), and discover new anti-inflammatory therapeutic targets for this disease.