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published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Zoology / Master / Master of Science

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Biochemistry / Master / Master of Science

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

Cyclopropenoid fatty acids (CPFA) are natural components of cottonseed oil, a major food oil in the United States. The ability of CPFA to cause abnormal biochemical and physiological effects when fed to laboratory and farm animals has prompted an investigation of their effects on mice. Between 0.05 and 0.55% CPFA were fed as glycerines of Sterculia foetida oil (SFO, containing 55% CPFA) to mice to determine their effect on certain aspects of growth, lipid metabolism and mitochondrial function. One-half percent SFO fed to weanling mice caused a small temporary decrease in growth rate when compared to controls. Many mice fed 1% SFO stopped growing and died by the end of a 9-week feeding trial. Mice fed less than 1% SFO, or 1% SFO for shorter periods of time, showed increased liver-to-body-weight ratios, accumulation of CPFA in adipose tissue and increased ratios of 16:0/16:1, 18:0/18:1 and total saturated to unsaturated fatty acids in liver and depot fat. Erythrocytes from CPFA-fed mice hemolyzed more slowly than erythrocytes from control mice in isotonicnonelectrolytes, implying an effect of CPFA on membrane lipid composition. One-half percent SFO fed for 9 to 31 days inhibited almost completely the incorporation of [¹⁴c] from labeled palmitate or acetate into liver monounsaturated fatty acids. At the same time, 0.5% SFO retarded the incorporation of label from acetate into ¹⁴C₂ and total liver lipid, but stimulated twofold the incorporation into liver sterols. The oxidation of labeled palmitate was also reduced. CPFA caused lipid accumulation in livers. P:0 ratios of liver mitochondria from mice fed 1% SFO for 6 to 15 days were 1.06- 1.45 while control P:0 ratios were 2.30-2.85. The decrease was due to decreased phosphorylation, but increased respiration. The relationship between the observed results and membrane fatty acid composition was discussed. / Graduation date: 1975

The relative enrichment of skin sebaceous gland lipids with deuterium-labeled α-tocopherol was compared with plasma enrichment to evaluate the delivery of vitamin E to skin. For the first week of this study, each subject consumed a daily dose of deuterated vitamin E (150 mg of an equimolar mixture of RRR-α-[5-(C²H₃)]-(d₃) and all rac-α-[5,7-(C²H₃)₂]-(d₆) tocopheryl acetates) with breakfast. Blood was drawn and skin lipids were collected daily for two weeks, then every other day for the following two weeks. Labeled and unlabeled vitamin E analysis was carried out using liquid chromatography and mass spectrometry (LC/MS). Skin cholesterol, plasma cholesterol and triglycerides were measured to evaluate changes in vitamin E levels relative to lipid content. While d₃ and d₆-α-tocopherols were found in plasma 24 h after the first dose, d₃-α-tocopherol was only detected in the skin sebaceous gland secretions after 1 week of supplementation. This data suggests a skin-mediated delivery system for vitamin E into skin lipid secretions. This finding is also supported by the observation that the ratio of α-to γ-tocopherol was greater in the skin than in the plasma. / Graduation date: 2002

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