LYSOPHOSPHATIDYLCHOLINE INCREASES APOLIPOPROTEIN-B SECRETION BY ENHANCING LIPID-SYNTHESIS AND DECREASING ITS INTRACELLULAR DEGRADATION IN HEPG2 CELLS

Free fatty acids and lysophosphatidylcholine (lysoPC) are the major li pids bound to human plasma albumin. The effects of fatty acids on the hepatic production of Apolipoprotein B (apo B) have been studied but t hose of lysoPC have not. In HepG2 cells, lysoPC increased apo B secret ion in different experiments by 50-120%, but did not affect the flotat ion properties of secreted lipoproteins. LysoPC affected neither the c ellular protein levels nor apo A-I secretion suggesting that its effec t was specific to apo B. Apo B secretion was maximum after incubating cells for 6 h with 0.2 mM lysoPC as equimolar fatty acid free bovine s erum albumin (BSA) complexes. LysoPC was metabolized by cells and its fatty acids were used for the synthesis of phosphatidylcholine and tri glycerides (TG). Experiments were performed to understand the mechanis m of lysoPC action. LysoPC increased the incorporation of H-3-glycerol into newly synthesized cellular (3-fold) and secreted (4-fold) trigly cerides, and increased the synthesis (40%) and secretion (4-fold) of p hospholipids. LysoPC did not affect apo B synthesis, but inhibited the intracellular degradation of apo B and increased its secretion. Triac sin C (5 mu M), an inhibitor of long chain acyl-CoA synthase, complete ly inhibited the induction of lipid synthesis and abolished the effect of lysoPC on apo B secretion. These studies indicated that lysoPC inc reased apo B secretion by inducing lipid synthesis; newly synthesized lipids probably protected apo B from intracellular degradation and enh anced secretion. These studies are consistent with the hypothesis that physiologic concentrations of lysoPC can be an important modulator fo r hepatic apo B secretion. (C) 1998 Elsevier Science B.V.