EnginEEring and natural SciEncES Triglyceride Regulation of Lysosomal Cholesterol in THP-1 Macrophages

The central question I investigated in my research this semester was how the cholesterol and triglyceride metabolic pathways interact in macrophages when cholesterol levels are high. What factors prevent or enhance macrophage ability to regulate cholesterol metabolism? We have preliminary evidence that excessive cholesterol accumulation in macrophages alters triglyceride metabolism in these cells. When cellular cholesterol levels are normal, the primary site of triglyceride hydrolysis is on the surface of the macrophage. There, lipases hydrolyze triglycerides within triglyceride-rich lipoproteins to glycerol and fatty acids. The fatty acids are carried across the cell membrane into the cytoplasm. In the cytoplasm, the fatty acids can be utilized to make triglycerides, phospholipids and cholesteryl esters. Cholesterol influences how the cell breaks down triglycerides. If cholesterol levels are high then triglyceride metabolism tends to occur more frequently in the lysosome. In contrast, when the cells have excess cholesterol, particularly within their lysosomes, the surface hydrolysis is suppressed and lipoproteins are taken up by endocytosis and delivered to lysosomes for hydrolysis. The effect of inhibiting the surface lipolysis was evaluated to determine the impact on intracellular cholesterol and triglyceride levels. The data indicates that the presence of triglyceride restores lysosomal metabolism of cholesterol.