Effect of dietary cholesterol on apolipoprotein E synthesis in the rabbit

Abstract

Female New Zealand White rabbits were fed either rabbit chow or rabbit chow plus 1% (w/w) cholesterol for 14 days. The chow-fed rabbits had normal plasma lipoprotein profiles on agarose gel electrophoresis, 59 ± 5 mg of cholesterol and 5.5 ± 0.4 mg of apolipoprotein E (apoE) per dl of serum. The cholesterol-fed rabbits had significant amounts of β-VLDL in their serum, 1870 ± 140 mg of cholesterol and 96 ± 12 mg of apoE per dl of serum. Relative rates of apoE synthesis were determined by incubating hepatocytes in culture medium containing [ 3H]leucine for 15 min at 37°C and expressing the radioactivity incorporated into immunoprecipitable apoE as a percentage of the radioactivity incorporated into total protein. Hepatocytes from cholesterol-fed rabbits had twice the relative rate of apoE synthesis (1.05 ± 0.18%) of hepatocytes from chow-fed rabbits (0.55 ± 0.07%). This increase in synthesis could be a major contributor to the 17-fold increase in serum apoE levels in the cholesterol-fed rabbit.