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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032609-05
Application #
3343997
Study Section
Metabolism Study Section (MET)
Project Start
1984-08-01
Project End
1992-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Freeman, D A; Ontko, J A (1992) Accumulation and mobilization of triglycerides and cholesteryl esters in Leydig tumor cells. J Lipid Res 33:1139-46
Ontko, J A; Cheng, Q; Yamamoto, M (1990) Metabolic factors underlying high serum triglycerides in the normal hamster. J Lipid Res 31:1983-92
Ontko, J A; Stiers, D L; Woodside, W F (1989) Formation of crystalline tripalmitin-rich spicules in isolated hepatocytes. J Lipid Res 30:1375-84
Azain, M J; Ontko, J A (1989) An explanation for decreased ketogenesis in the liver of the obese Zucker rat. Am J Physiol 257:R822-8
Ontko, J A; Wang, C S (1989) Elevation of liver diacylglycerols and molecular species of diacylglycerols in rats fed a lipogenic diet. J Lipid Res 30:691-9
Woodside, W F; Ontko, J A (1989) Regulation of triglyceride mobilization in isolated hepatocytes by dibutyryl cyclic AMP and epinephrine. J Cardiovasc Pharmacol 13 Suppl 2:S38-44;discussion S44
Ontko, J A; Woodside, W F (1989) Influence of doxazosin on lipid transport in rats and hamsters. J Cardiovasc Pharmacol 13 Suppl 2:S31-6;discussions 36-7
Brindle, N P; Ontko, J A (1988) Alpha-adrenergic suppression of very-low-density-lipoprotein triacylglycerol secretion by isolated rat hepatocytes. Biochem J 250:363-8
Yamamoto, M; Yamamoto, I; Tanaka, Y et al. (1987) Fatty acid metabolism and lipid secretion by perfused livers from rats fed laboratory stock and sucrose-rich diets. J Lipid Res 28:1156-65
Ontko, J A; Perrin, L W; Horne, L S (1986) Isolation of hepatocellular lipid droplets: the separation of distinct subpopulations. J Lipid Res 27:1097-103

Showing the most recent 10 out of 15 publications