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In this study we have investigated, in four normal males the effects of dietary saturated and polyunsaturated fat on the chemical composition and thermotropic properties of human high density lipoproteins (HDL) and have measured the influence of the diets on the metabolism of that fraction of HDL apolipoprotein A-I (apoA-I) that undergoes exchange in vitro and accounts for approximately two-thirds of the lipoprotein's apoA-I complement. When compared with the saturated fat diet, the polyunsaturated diet reduced plasma cholesterol (24%, P &lt; 0.01) by affecting the cholesterol content in the very low density lipoprotein ( downward arrow25%, P &lt; 0.02), low density lipoprotein ( downward arrow20%, P &lt; 0.01), and high density lipoprotein fractions ( downward arrow33%, P &lt; 0.01). Plasma triglyceride was also lowered (by 13%, P &lt; 0.01). Furthermore, polyunsaturated fat ingestion caused a significant fall in the palmitate and stearate content of HDL triglyceride (41 and 37%, respectively), cholesteryl esters (29 and 35%), and phospholipids (17 and 9%) with a concomitant increase in the linoleate content of these moieties (157, 28, and 29%, respectively). The polyunsaturated diet also produced reciprocal changes in the percentage protein ( downward arrow9%, P &lt; 0.02) and phospholipid ( downward arrow11.5%, P &lt; 0.01) in HDl. These compositional changes were associated with an increase in the microscopic fluidity of the polyunsaturated HDL, although both diets had little effect on the fluidity parameters of HDL at body temperature. Rate zonal ultracentrifugation indicated that the HDL(2)/HDL(3) ratio fell by 28% (P &lt; 0.05) on the polyunsaturated fat diet. In addition to the above, this diet reduced plasma apoA-I by 21% (P &lt; 0.01). No change was seen in the fractional catabolic rate or the distribution of the apoprotein between intravascular and extravascular compartments on the two diets. However, when compared with the saturated diet, the synthetic rate of apoA-I was reduced by 26% during polyunsaturated fat feeding. The results show that polyunsaturated fat alters the chemical composition, thermotropic properties, and subfraction distribution of HDL without changing the fractional rate of catabolism of their major protein, apoA-I.These findings deserve careful consideration in determining the applicability and efficacy of polyunsaturated fat diet therapy in the prevention of atherosclerosis in man.

Effects of Dietary Polyunsaturated and Saturated Fat on the Properties of High Density Lipoproteins and the Metabolism of Apolipoprotein A-I