Storage of retinyl esters in hepatic stellate cells: The role of LRAT in stellate cell lipid droplet formation

Hepatic stellate cells represent 5–8% of the total number of cells in a healthy liver and are responsible for the majority of the liver's retinoid stores. Retinyl esters are stored within the characteristic lipid droplets of these cells and comprises 40% of the droplets total lipid content along with triglycerides, phospholipids, cholesterol esters, cholesterol and free fatty acids. The amount of stored retinyl ester decreases progressively in liver injury when stellate cells are activated. We investigated the role of the enzyme Lecithin:Retinol Acyl Transferase (LRAT) and show that it is the most important enzyme for catalyzing the formation of retinyl esters in the majority of tissues in the body. LRAT knockout (KO) mice have undetectable levels of retinyl esters in their livers and depend on regular intake of retinoids to maintain their health. Livers examined by electron microscopy showed no lipid droplets in their hepatic stellate cells. Yet these mice showed no signs of fibrosis. showed earlier signs of hepatic fibrosis compared to wild type controls. Our studies indicate a novel role for LRAT in However, LRAT KO mice challenged with CCl 4 the formation of lipid droplets in the hepatic stellate cell, and possibly in other cells, and this can make the mice more susceptible to experimentally induced liver fibrosis.