Abstract 20520: A New Lysosome-Mediated Degradation Mechanism for Hepatic Lipid Droplets Turnover

Dietary supplementation with fish oil, rich in n-3 fatty acids such as EPA (20:5n-3), has been shown in many studies to exert a hypotriglyceridemic effect by reducing both plasma triglycerides (in the form of VLDL) and intrahepatic triglycerides (presented in cytoplasm as lipid droplets). To date, no cellular or molecular mechanisms have been defined to explain the hypotriglyceridemic action of n-3 fatty acids. Intrahepatocellular triglycerides are an important contributor to plasma fatty acids and lipoproteins level. We have discovered a direct interaction between lysosome and lipid droplets, in a Kiss-and-run fashion, as the principal mechanism for the lipid droplets turnover upon EPA treatment. Inactivating lysosome function or disrupting lysosome movement resulted in accumulation of lipid droplets under EPA treatment conditions, whereas inactivating the known lipolysis enzymes ATGL or HSL was unable to attenuate droplets turnover. Lipophagy has been reported as a selective autophagic mechanism for deg...