Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.
Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Influence of dietary fatty acids on hepatic lipoprotein composition and secretion
Coronary heart disease continues to be the leading cause of death in the United States. This study was conducted to determine the effects of dietary fatty acids on hepatic lipoprotein composition and secretion. Additionally, the effects of antisense DNA for ACAT1 and ACAT2 were examined on lipoprotein composition and secretion rate. HepG2 cells were loaded with six different fatty acids (oleic, linoleic, elaidic, stearic, CLA and palmitic) bound to BSA added to serum containing HAM F-10 media and incubated for 24 h. The media, which was a serum-free HAM F-10, was collected from the cells. Oleic acid was the only fatty acid to significantly altered apoB100 secretion rate. However, palmitic and elaidic acids significantly decreased the secretion rates of free cholesterol when compared to control cell cultures. Palmitic acid caused a significant decrease in phospholipid secretion rate and elaidic acid caused a significant decrease in the secretion rate of triglycerides. When elaidic acid was incubated in HepG2 medium, the particle size significantly decreased compared to the control (70 ± 3.0 and 94 ± 6.8, respectively). Antisense DNA specific for ACAT1 and ACAT2 genes were developed to block the transcription and inhibit protein formation of ACAT1 and ACAT2. HepG2 cells were loaded with varied amounts (0 ng, 18 ng, 112 ng, 180 ng) of ACAT1 or ACAT2 antisense added to DMEM-HAM F-10 medium and incubated for 24 hours. ApoB100 and free cholesterol secretion were significantly decreased compared to control cells when antisense DNA for ACAT1 and ACAT2 were added to cultures. Additionally, the surface lipids (phospholipids:apoB100 and free cholesterol:apoB100) were significantly decreased (P < 0.05). Antisense DNA for ACAT1 decreased cholesteryl ester:apoB when compared to the control (769 ± 72.3 and 806 ± 136.8). Together, the surface and core lipids of the lipoprotein particle contribute to underlying particle size, which sways cardiovascular development. These overall findings put us one step closer to combating the U.S. epidemic of CHD. ^
Biology, Molecular|Health Sciences, Nutrition
Mitmesser, Susan Hazels, "Influence of dietary fatty acids on hepatic lipoprotein composition and secretion" (2003). ETD collection for University of Nebraska - Lincoln. AAI3092574.