Distribution of cholesterol and triglycerides among lipoprotein fractions in fat-fed rabbits at different levels of serum cholesterol.

The serum lipoproteins of rabbits given semisynthetic cholesterol-free diets containing coconut oil or butter or a conventional rabbit chow supplemented with cholesterol, were studied by preparative ultracentrifugation and electrophoresis. (1) All three diets elevated the total cholesterol level but only the coconut oil diet markedly increased the triglyceride (TG) content in addition. All ultracentrifugation fractions showed elevated cholesterol/TG ratios, and this was especially evident for the cholesterol diet. In the hyperlipidemic rabbits cholesterol was therefore mainly transported in lipoproteins with a changed lipid composition. (2) The lipid levels of the "HDL" fraction were more or less unaffected by the lipid concentration in whole serum. In the total serum cholesterol ranges 150-500 (coconut oil diet) and 100-300 mg/100 ml (cholesterol diet), most cholesterol was transported as "LDL" cholesterol. This latter fraction reached maximum cholesterol concentrations of about 350 (coconut oil diet) and 400 mg/100 ml (cholesterol diet) at total cholesterol levels of approximately 600 and 1200 mg/100 ml serum, respectively. At still higher levels of total cholesterol, the whole increment was concentrated to the "VLDL" fraction. (3) With semisynthetic diets in the whole cholesterol range 250-400 mg/100 ml it was possible, with respect to cholesterol, to induce fairly similar concentrations and distributions to those seen in man, with about 60% transported as "LDL", 30% as "VLDL" and 10% as "HDL" cholesterol with the coconut oil diet and 65%, 20% and 15%, respectively, with the butter diet. Such experimental conditions seem to be suitable for testing the hypocholesterolemic action of drugs intended for human hyperlipidemia Type II. (4) Compared with earlier investigations on rabbits, the present distribution study suggests that the degree of aortic lipid infiltration in cholesterol-fed rabbits is better related to the levels of "LDL" than to "VLDL" cholesterol.