Role of extracellular vesicles in non-alcoholic fatty liver disease

Once thought to be a benign accumulation of hepatic fat, non-alcoholic fatty liver disease (NAFLD) is now recognised as a prevalent complication of obesity with serious consequences if left untreated. This includes liver inflammation and impaired glucose metabolism, and with time may result in cirrhosis and organ failure. While basic diagnostic tools exist, such as ultrasound and serum protein markers, these are often unreliable and warrant the use of more invasive techniques such as tissue biopsy. Given most patients only become symptomatic once the disease is advanced, there is an urgent need to develop a better diagnostic strategy for NAFLD. This project aims to address the issue by exploring a novel biomarker candidate: extracellular vesicles (EVs). These submicron vesicles can be isolated from the circulation and tracked back to their parent cells by nature of their surface markers. EVs are constitutively released by all cell types, however, their abundance and molecular cargo are shown to be changed in various conditions and disease states, which also affects the functions they mediate as “intercellular messengers”. Using rodent models of diet-induced NAFLD, we aim to determine whether plasma or liver-derived EVs could be effectively used as a marker for the progression of NAFLD, and whether suitable interventions exist to slow or even reverse the disease. Finally, using in vitro models of hepatocyte EV uptake, the project will also investigate how EVs impart signals within the liver, in a paracrine fashion and from extraheptic tissue