Rapid stimulation of apolipoprotein B secretion by oleate is not associated with cholesteryl ester biosynthesis in...

Intracellular cholesteryl ester (CE) biosynthesis is thought to play an important role in the secretion of apolipoprotein (apo) B from hepatocytes. We have reported that oleate rapidly increased apo B secretion by suppressing early intracellular degradation of nascent apo B in HepG2 cells. The aim of the present study is to determine whether the rapid stimulatory effect of oleate on apo B secretion is associated with CE biosynthesis. Oleate (0.4 mM) rapidly and strikingly increased triacylglycerol (TG) but not CE in the cells and the medium. Apo B was linearly secreted into the medium during 180 min and oleate doubled the rate of secretion. Fluvastatin, a newly synthesized 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, or 25-hydroxycholesterol did not alter the apo B secretion rate, although the former suppressed and the latter stimulated CE production in the cells. Pulse-chase studies revealed that neither fluvastatin or 25-hydroxycholesterol treatments affected apo B production or intracellular degradation of newly synthesized apo B. These results suggest that, at least in short-term incubation, the modulation of CE biosynthesis does not alter apo B kinetics in HepG2 cells. Therefore, we concluded that rapid stimulation of apo B secretion by oleate is not associated with CE biosynthesis.