As a consequence of the results of a recent clinical trial there has been an amplified effort to restrict the dietary intake of fats and cholesterol. In spite of this recommendation, little is known of the long term effects of various kinds of dietary fat on the structure, composition, and metabolism of plasma lipoproteins in normal adults. The overall goal of this proposal is to determine the effects of four kinds of dietary fat on plasma lipoprotein structure and metabolism. These diets are within the guidelines of current recommendations with respect to both fat and cholesterol content but differ in the quality of fatty acids that compose them. They are 1) a Western type saturated fat diet, 2) the Asian or polyunsaturated diet, 3) the monounsaturated or Mediterranean diet, and 4) a diet enriched in n-3 fatty acids which is common to certain maritime communities. Each subjects will be kept on these diets for three months during which several key markers of lipid metabolism will be followed. These include the plasma levels of total and esterified cholesterol; triglycerides; high, low and very low density lipoprotein cholesterol; and apolipoproteins A-I, A-II, B and E. At the end of the 3 months, a unit of blood will be collected and complete compositional and structural analyses of the plasma lipoproteins and several key proteins related to lipid metabolism will be performed in addition to those cited above. All lipoproteins will be isolated and analyzed with respect to their apolipoprotein and lipid content. Each lipid class will be further analyzed with respect to its fatty acid composition. The structure of each lipoprotein will be evaluated by hydrodynamic, spectroscopic, and thermodynamic methods. The activities of lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein and phospholipid transfer protein will also be measured. The response of each subject to standard oral fat loads that simulate the fatty acid composition of the four test diets will be conducted to determine the effects of a long-term dietary regimen of a specific kind of fat on the mechanism and rate of clearance of similar or dissimilar fats.
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