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 and pathological conditions and are also a function of the cell type. This investigation will focus on the hepatocyte and cytoplasmic lipid droplets rich in triglyceride. These lipids provide fatty acids for energy, the synthesis of membrane phospholipids and the production of secretory lipoproteins. However, little is known about the mechanism(s) by which the lipids in these droplets are mobilized. This project will define the intracellular site(s) of lipolysis, whether cytosolic, lysosomal, endoplasmic retriculum or elsewhere, and will determine if carrier proteins or other translocation processes facilitate the mobilization of droplet 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. It will also be determined whether cholesterol esters are mobilized from hepatocellular lipid droplets in a process similar to that found to characterize triglyceride release. It will then be determined if analogous mechanisms are operative in the mobilization of lipid droplet triglyceride and cholesterol ester in other cellular systems, namely in myocytes, smooth muscle cells, macrophages and fibroblasts. The size and number of lipid droplets in the cell cytoplasm is determined by the relative rates of formation anad 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.
Showing the most recent 10 out of 15 publications
