Lipid droplets occur in the cytoplasm of many cell types. The major constituents of these lipid droplets are triglyceride and cholesterol ester. The abundance and lipid composition of these droplets are influenced by nutritional, hormonal, genetic, and pathological conditions. This investigation will focus on the hepatocyte and cytoplasmic lipid droplets rich in triglyceride. These lipids provide fatty acids for energy, synthesis of membrane phospholipids and production of secretory triglyceride-rich lipoproteins. However, little is known about the mechanism(s) by which the lipids in these droplets are mobilized. Rat liver, and cellular and subcellular systems derived therefrom, will be employed. New methodology developed here for the isolation of different populations of triglyceride-rich particles will be utilized. This project will define the intracellular site(s) of lipolysis, whether cytosolic, lysosomal, endoplasmic reticulum or elsewhere, and will determine if carrier proteins or other translocation processes facilitate the mobilization of droplets lipids. The lipolytic enzyme will be identified. The possible """"""""en bloc"""""""" transfer of a portion of the droplet triglyceride to the assembly of triglyceride-rich secretory lipoproteins will be examined. The possible involvement of the cytoskeleton in droplet lipid mobilization will be explored. The factors which regulate the rate of mobilization of triglyceride from the droplet pool will be investigated in hepatocytes isolated from rat liver. It will also be determined whether cholesterol esters are mobilized from hepatocellular lipid droplets in a process similar to that found to characterrize triglyceride release. The size and number of lipid droplets in the cell cytoplasm is determined by the relative rates of formation and mobilization. The mechanisms of mobilization to be studied in this project have bearing on pathological conditions in which these droplets accumulate, including the development and potential regression of lipid deposits in foam cells of atherosclerotic lesions.
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