BUTYRATE STIMULATES THE SECRETION OF APOLIPOPROTEIN B-100-CONTAINING LIPOPROTEINS FROM HEPG2 CELLS BY INHIBITING THE INTRACELLULAR DEGRADATION

We have shown previously that sodium butyrate induces a 2-fold increas e in the secretion of apo B-100 by HepG2 cells. The apo B-100 mRNA lev el was not changed in butyrate-treated cells, indicating regulation at the translational or co- or posttranslational level (Biochem. J. (199 1) 278, 557-564). In this paper, the mechanism by which butyrate incre ases apo B-100 secretion was further investigated. Pulse-chase analysi s showed that in control incubations only 18 +/- 4% of the total amoun t of labelled apo B-100, present intracellularly after a 10 min pulse period, was secreted after a 90 min chase period, indicating that the major part of newly synthesized apo B-100 is degraded intracellularly. After addition of butyrate the secreted amount increased to 32 +/- 6% of the total synthesized amount. Treatment of HepG2 cells with butyra te resulted in an enhanced intracellular concentration of triacylglyce rols (+30%), with no or only a marginal effect on the cellular content of cholesterol and cholesteryl esters. Secretion of triacylglycerols (+90%) and cholesteryl esters (+78%), but not of cholesterol, was incr eased to the same extent as apo B-100 secretion (+102%). The total mas s of triacylglycerols, i.e., the sum of triacylglycerols present intra cellularly and secreted by HepG2 cells, was significantly increased up on incubation with butyrate (+32%), whereas the total mass of choleste ryl esters was not affected. Butyrate did not affect the buoyant densi ty of apo B-100-containing lipoproteins secreted by HepG2 cells. These results suggest that an increased availability of triacylglycerols, f ormed after the addition of butyrate regulates the amount of apo B-100 degraded intracellularly and consequently apo B-100 secretion.