Role of ATG14 in the regulation of hepatic function

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Project Summary 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.