Effect of ethanol on the synthesis and secretion of apoA-I- and apoB-containing lipoproteins in HepG2 cells

The short- and long-term effects of ethanol on the production of lipids and apolipoproteins (apo) in HepG2 cells were studied. Short-term incubation with 1% ethanol caused a significant 32% increase in the cellular content of both triglycerides and cholesteryl esters. Under these conditions, the net accumulation in the medium of triglycerides, unesterified cholesterol, cholesteryl esters, apoA-I, and apoE was stimulated by 75%, 41%, 43%, 19%, and 39%, respectively. ApoA-I and apoE mRNA levels increased by 15%. The major short-term effect of ethanol was on the net accumulation of apoB in the medium which was stimulated by 56-100% in the presence of 0.1-1.0% ethanol. Under these conditions, apoB mRNA abundance was elevated by 17-26% and LDL receptor activity was unchanged. The increase in apoB accumulation in the medium was predominantly due to augmented secretion of newly synthesized apoB-100 which was evident at 0.05% ethanol. The secretion of newly synthesized apoA-I was not altered by short-term incubation with < or = 0.5% ethanol. The rate of apoB production was positively correlated with the cellular and secreted cholesteryl esters and secreted triglycerides. Addition of Pfizer CP-113,818, an inhibitor of acyl-CoA:cholesterol acyltransferase, caused a 69% reduction in the secretion of cholesteryl esters and a 24% decrease in that of apoB-100. In contrast to the short-term effect of ethanol, long-term incubation with ethanol resulted in a dose-dependent increase in the secretion of newly synthesized apoA-I without significantly affecting that of apoB-100. The increase in apoA-I secretion was evident at 0.05% ethanol and reached a maximum of 77% at 0.5% ethanol. These observations indicate that in HepG2 cells the effect of ethanol on the production of apoA-I- and apoB- containing lipoproteins is both time- and dose-dependent and is different in these two apolipoproteins.