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 increase in the secretion of apo B-100 by HepG2 cells. The apo B-100 mRNA level was not changed in butyrate-treated cells, indicating regulation at the translational or co- or posttranslational level (Biochem. J. (1991) 278, 557-564). In this paper, the mechanism by which butyrate increases apo B-100 secretion was further investigated. Pulse-chase analysis showed that in control incubations only 18 +/- 4% of the total amount 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 butyrate resulted in an enhanced intracellular concentration of triacylglycerols (+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 increased to the same extent as apo B-100 secretion (+102%). The total mass of triacylglycerols, i.e., the sum of triacylglycerols present intracellularly and secreted by HepG2 cells, was significantly increased upon incubation with butyrate (+32%), whereas the total mass of cholesteryl esters was not  affected. Butyrate did not affect the buoyant density of apo B-100-containing lipoproteins secreted by HepG2 cells. These results suggest that an increased availability of triacylglycerols, formed after the addition of butyrate regulates the amount of apo B-100 degraded intracellularly and consequently apo B-100 secretion.
Kaptein
A
A
Gaubius Laboratory IVVO-TNO, Institute of Ageing and Vascular Research, Leiden, The Netherlands.
de Wit
E C
EC
Princen
H M
HM
D000418:Albumins / Q000096:biosynthesis*; D016632:Apolipoprotein A-I / Q000096:biosynthesis*; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line / Q000187:drug effects; D006801:Humans
D000418:Albumins; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D002087:Butyrates; D020148:Butyric Acid