Effects of oleate and insulin on the production rates and cellular mRNA concentrations of apolipoproteins in HepG2 cells.

We have reported previously that, in HepG2 cells, there is a lack of coordinate induction of triglyceride and apolipoprotein (apo) production by oleate and that insulin inhibits the production of triglyceride-rich, apoB-containing lipoproteins. The aim of the present study was to determine whether the effects of oleate and insulin on the net accumulation of apolipoproteins, specifically apoB, were related to their cellular mRNA concentrations. It was first established that the production of triglyceride-rich, apoB-containing lipoproteins and the concentration of mRNA for apolipoproteins A-I, A-II, B, and E were not affected by increasing the glucose concentration of medium from 5.5 to 20 mM. Oleate and insulin had no effect on either the accumulation in the medium or the cellular mRNA concentration of apolipoproteins A-I and A-II. On the other hand, the addition of oleate caused a two- to threefold increase in the accumulation of triglycerides in the medium without significantly affecting either the rates of accumulation or cellular mRNA levels of apolipoproteins B and E. In the presence of insulin, there was a dose-dependent decrease in the net accumulation of triglycerides and apoB and, to a lesser extent, cholesteryl esters and apoE. This inhibitory effect of insulin on the accumulation of triglycerides and apoB was partially abolished after a prolonged exposure of cells to insulin. Under these experimental conditions and at all concentrations tested, insulin had no effect on the cellular concentration of mRNA for either apoB or apoE.(ABSTRACT TRUNCATED AT 250 WORDS)