Nonalcoholic fatty liver disease (NAFLD) affects over 30% adults in the US. The NAFLD initially manifests as hepatic steatosis and progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and even cirrhosis or hepatocellular carcinoma. Due to the progressive nature of the disease, it is crucial to understand the early pathogenic events of the NAFLD development. Among those early events, abnormal lipid metabolism is largely responsible for the hepatic steatosis that is manifested as extra triglyceride accumulation in the liver in the form of lipid droplets. Triglyceride homeostasis is a very dynamic process as it involves both biosynthesis and breakdown. The lipid droplet mobilization remains poorly understood. In this application, the research team will investigate the regulatory mechanisms of lipid droplet breakdown in cellular and animal models with a focus on a key autophagy regulator ? autophagy related 14. It is expected that the proposed research will provide key mechanistic insights into the strategy for therapeutic intervention and treatment of NAFLD.
The proposed research in this application is relevant to public health because better understanding of the pathogenesis of fatty liver disease is ultimately expected to provide potential novel drug targets for the prevention and treatment of this health problem. Thus, this project is relevant to the part of NIH?s mission that pertains to pursuing fundamental knowledge that will help extend healthy life and reduce the burdens of illness.
