REGULATION OF HIGH DENSITY LIPOPROTEIN METABOLISM BY CHOLESTEROL AND JOJOBA OILS

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High density lipoproteins (HDL) are believed to be anti-atherogenic, because they remove excess cholesterol from peripheral cells and transport it through the circulatory system as cholesteryl esters to the liver where it is degraded. This reverse cholesterol transport process is important in regulating intracellular and plasma cholesterol concentrations and, thereby, the development of atherosclerosis. When rabbits are fed dietary cholesterol and/or dietary jojoba oil, HDL cholesterol (HDL-C) concentrations decrease in the cholesterol-fed rabbits, increase in the jojoba oil-fed rabbits, and do not change in the cholesterol + jojoba oil- fed rabbits. The long-term objective of this research project is to provide a biochemical explanation for the opposing actions of these two dietary factors. Since apolipoprotein A-I (apoA-I) and total cholesterol (free cholesterol + cholesteryl ester) are major components in HDL particles, they will be used as models of how cholesterol and jojoba oil regulate the levels of a protein and a lipid present in these particles. The specific aims of the research project are to quantitate the changes in apoA-I and total cholesterol concentrations in the serum, in the HDL fraction, and in the HDL2 and HDL3 subclasses of the HDL fraction from New Zealand White rabbits. These animals will be fed either a normal diet or one supplemented with 1% cholesterol or 2% jojoba oil or 1% cholesterol+2% jojoba oil for 21 days, and blood will be collected at predetermined times throughout the experiment. ApoA-I and total cholesterol concentrations will be quantified with an enzyme-linked immunosorbent assay (ELISA) and an enzymatic cholesterol assay, respectively. These measurements will identify those lipoproteins whose apoA-I and total cholesterol concentrations are changing and will measure the rate, the magnitude, and the sequence of these changes. This research will also determine the relative rates of apoA-I synthesis in small intestine mucosal cells from these animals. A monospecific antisera for rabbit apoA-I will be used to quantitatively immunoprecipitate apoA-I from labeled small intestine mucosal cells in order to determine if dietary cholesterol and dietary jojoba oil regulate the rate of apoA-I synthesis in this organ. The fulfillment of these objectives will provide useful information about the biochemical mechanism by which dietary factors regulate apoA-I and total cholesterol concentrations in the blood of the rabbit and, thereby, provide a better biochemical understanding of how dietary factors regulate HDL metabolism in this animal as well as its possible regulation in humans.