Effects of a High Cholesterol Diet on Synthesis of Plasma Low Density Lipoprotein. ∗

When diets high in fat and cholesterol are fed to animals, plasma cholesterol levels are elevated. In some species, such as the rabbit, the levels reached are very high and atherosclerosis readily develops(l). Under these circumstances, the low density or β lipoprotein levels in plasma are particularly increased. It is difficult to elevate the plasma low density lipoproteins in the rat to this degree by feeding such diets, but there is no doubt that elevation of plasma and liver cholesterol content can be achieved(2). Can such diets affect the rate of hepatic synthesis of the low density lipoproteins in the rat? We have recently succeeded in measuring the net synthesis of plasma low density lipoproteins in the perfused rat liver by an immunochemical method(3) and have now applied this technic to an investigation of the effects of a high fat-high cholesterol diet. Our results indicate that, in the rat, such a diet does not lead to an increased synthesis of the protein moiety of the low density lipoproteins but does increase the amount of cholesterol present in the lipoprotein molecule released by the liver during perfusion in vitro.

Materials and methods. The rats used were of the Wistar strain, weighing between 270 and 300 g, and were fed for 3 weeks on a commercial “cholesterol-free” diet (Nutritional Biochemicals Corp.) containing either 15% of added Wesson oil or 15% of Wesson oil plus 5% of cholesterol. The livers were perfused for 1 hour at 37° with a suspension of rat red cells in Krebs-Ringer-bicarbonate medium as previously described(3,4) and the amount of low-density lipoprotein measured by means of the quantitative precipitin reaction with an antiserum prepared in the goat. The immune precipitate was analyzed for its cholesterol(5) and protein(6) content, thus affording a measure of the synthesis of both cholesterol and protein moieties.