Dietary cholesterol does not affect the synthesis of apolipoproteins B and E by rat hepatocytes

To examine the unproved hypothesis that dietary cholesterol affects the synthesis of apolipoprotein B and E, we fed rats a cholesterol-rich diet that has been shown to alter dramatically the serum concentrations of these apolipoproteins. Rats fed for 4 weeks on a cholesterol-rich diet accumulate increased concentrations of low Mr 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. Thus there was a discordance between the effects of dietary cholesterol on serum apolipoprotein concentrations and hepatocyte synthesis and secretion. The data indicate that altered hepatic apolipoprotein synthesis cannot account for the changes in serum apolipoprotein concentrations caused by dietary cholesterol.