Rapid stimulation of apolipoprotein B secretion by oleate is not associated with cholesteryl ester biosynthesis in HepG2 cells.

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.