DIETARY-CHOLESTEROL DOES NOT AFFECT THE SYNTHESIS OF APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E BY RAT HEPATOCYTES

To examine the unproved hypothesis that dietary cholesterol affects the synthesis of apolipoprotein B and E, rats were fed a cholesterol-rich diet that dramatically alters the serum concentrations of these apolipoproteins. Rats fed for 4 wk on a cholesterol-rich diet accumulate increased concentrations of low MW apolipoprotein B (+ 2.7-fold) and decreased concentrations of apolipoprotein E (-40%) in their serum. Hepatocytes obtained from similarly treated rats were placed in monolayer culture and the rate of synthesis de novo of apolipoproteins was determined. Although cells from cholesterol-fed rats remained filled with lipid droplets throughout the experimental period, there was no difference in plating efficiency or viability, compared with cells obtained from chow-fed control rats. Both groups of cells synthesized and secreted immunoprecipitable apolipoproteins B and E at similar rates throughout the 18 h experiment. There was a discordance between the effects of dietary cholesterol on serum apolipoprotein concentrations and hepatocyte synthesis and secretion. Altered hepatic apolipoprotein synthesis cannot account for the changes in serum apolipoprotein concentrations caused by dietary hypercholesterolemin.