No description available.

xii, 230 p. : ill. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Physiology, 1973

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Animal Physiology, 1973.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

The metabolic fate of cholesterol delivered to rat hepatocytes by rat plasma lipoproteins was determined. Binding and degradation of rat low and high density lipoproteins (LDL and HDL) in rat hepatocytes were studied. ¹²⁵I-labelled LDL and HDL were incubated with cells in the presence of varying concentrations of unlabelled lipoproteins for two hours at 37°C. The amount of ¹²⁵I-LDL and ¹²⁵I-HDL binding and degradation decreased by increasing concentrations of respective unlabelled lipoproteins. The presence of 50-fold excess of unlabelled LDL or HDL resulted in a reduction of ¹²⁵I-LDL and ¹²⁵I-HDL bindings by 66-82%, and degradations by 63-88%, respectively. Equilibrium dissociation constants (K [subscript d]) determined by Scatchard analysis for HDL (.15 x 10⁻⁸M) and LDL (1.04 x 10⁻⁸M) revealed that HDL have approximately 7-fold higher binding affinity for receptors on cell surface than LDL. Specific use of LDL and HDL-cholesterol for bile acid synthesis by rat hepatocytes was investigated. When LDL and HDL labelled with ³H-LDL cholesterol was transformed to bile acids mostly as lithocholic, chenodeoxy and deoxycholic acids. A technique developed for isolation of hepatocytes from rat liver was described. Once isolated by the technique most cells retained their microscopic structural integrity, and excluded trypan blue. The viability was 93%, which decreased to 86% after four hours of incubation. The presented data demonstrated that both HDL and LDL bind to specific receptors on hepatocytes and undergo proteolytic degradation in rats. The study also showed that the binding affinity of HDL to hepatic receptors was much greater than that of LDL but in total binding LDL uptake was four times greater than HDL, suggesting the presence of two specific binding sites for HDL and LDL. The first direct evidence for the preferential utilization of HDL-cholesterol for biosynthesis of bile acids in vivo is presented. This finding is compatible with the current concept of HDL as the protective lipoprotein against developing coronary heart disease. / Graduation date: 1985

No description available.

Phytosterols occur naturally in the non-saponifiable material of plant oils. Sitostanol, the saturated derivative of beta-sitosterol, is found in negligible concentrations in plant sources and, hence, is almost absent from typical Western diets. Tall oil extracts, on the other hand, contain about 20% (w/w) sitostanol. Phytosterols have been shown to lower plasma total cholesterol levels in animals and humans while sitostanol exhibited stronger reducing effects. Several studies have suggested that phytosterols lower plasma total cholesterol levels by either inhibiting cholesterol absorption or altering the activities of enzymes critical in cholesterol metabolism and excretion. However, results obtained demonstrate inconsistency regarding the effects of phytosterols on cholesterol absorption rates and cholesterogenesis. In addition, few studies have determined quantitatively the changes in the rate of cholesterol absorption and biosynthesis. Hence, the objective of this thesis was to investigate further the impact of different sources of phytosterols on plasma lipid profiles and to develop a new methodology for simultaneous measurement of percent cholesterol absorption and cholesterol synthesis rates in animals and humans. The stable isotopes, 13C-, 18 O-cholesterol, and deuterium oxide were utilized for the dual isotope plasma ratio and deuterium uptake methodologies. Results from the series of animal experiments conducted demonstrate (i) a gender effect of phytosterols in modulating plasma lipid profile in hamsters, (ii) that sitostanol was more potent in lowering plasma and hepatic lipid concentrations than beta-sitosterol in hamsters and rabbits and (iii) that this lowering effect was due to a reduction in fractional cholesterol absorption and an increase in cholesterol excretion rates. Concomitantly, an up-regulation in cholesterogenesis was observed in hamsters. Furthermore, in humans tall oil phytosterols lowered total cholesterol levels in hypercholesterole

Phytosterols play an important role in nature and as synthetic supplements for the modification of cholesterol metabolism in humans. The consensus is that the primary mechanism by which phytosterols modify lipid profiles is through altering the absorption of cholesterol. This thesis examined the effects of phytosterol mixtures on (i) de novo cholesterol synthesis rates and appearance of de novo cholesterol into the cholesterol ester pool through the use of deuterium incorporation, as well as, (ii) plasma lipid and sterol concentrations in normolipidemic humans. The initial investigation of this thesis compared the effects of diets based on either corn oil, olive oil, or olive oil plus phytosterol mixture on cholesterol metabolism. Each treatment was administered for 10 days in a cross-over design to 16 normolipidemic humans. In addition to confirming prior conclusions that corn oil was more effective than olive oil at decreasing plasma total and LDL-cholesterol concentration, this study was one of the first to determine that the differential effects on cholesterol metabolism observed in humans consuming corn versus olive oil is due, in part, to the higher concentrations of plant sterols naturally found in corn oil. The second study presented in this thesis investigated the differential effects on sterol metabolism of phytosterol mixtures either enriched with sitostanol or sitostanol-free administered for 10 days in 11 normolipidemic humans. The results of this study demonstrated that only the phytosterol mixture containing low doses of sitostanol decreased plasma total and LDL-cholesterol concentrations and increased the circulating HDL/LDL ratios; thus, the sitostanol-enriched phytosterol mixture was a more effective cholesterol-lowering agent.