Lipid-Laden Macrophages Downregulate AKT Phosphorylation and Metabolize Lipid Droplets via Autophagy
Thesis - Open Access
Master of Science (MS)
Department / School
Biology and Microbiology
Macrophages contribute to plaque formation in atherosclerosis. Macrophages take up modified low-density lipoproteins and store excess cholesterol and triglycerides in lipid droplet organelles. Evidence of lipid-laden macrophages or “foam cells” is apparent on histology sections of diseased arteries, and this lipid-laden appearance can be recreated in cell culture upon exposure of cultured macrophages to acetylated LDL (Ac-LDL). Under nutrient stress, neutral lipids in lipid droplets are hydrolyzed by lipolysis, autophagy, or both. However, these processes are not well understood in macrophages. We created lipidladen macrophages by 24-h exposure to Ac-LDL and analyzed dynamics of lipid droplet metabolism following removal of Ac-LDL from cell culture medium. We found that lipid droplets in these macrophages are cleared within 24 h of Ac-LDL removal from the medium. We then analyzed co-localization of adipophilin, a lipid droplet marker, and LC3, an autophagy marker, with lipid droplets. Results from induction of autophagy by rapamycin, and inhibition of autophagosome formation by 3-methyl adenine suggests the involvement of autophagy in lipid droplet disappearance from cells in the absence of Ac- LDL in the culture media. Studying the mechanisms of lipid droplet degradation will allow us to understand how lipid droplets could be cleared from foam cells resident in atherosclerotic plaques and identify potential therapeutic targets for treating atherosclerosis.
Library of Congress Subject Headings
Includes bibliographical references
Number of Pages
South Dakota State University
Sultana, Rifat, "Lipid-Laden Macrophages Downregulate AKT Phosphorylation and Metabolize Lipid Droplets via Autophagy" (2017). Electronic Theses and Dissertations. 1743.