FATTY-ACIDS MODULATE LECITHIN-CHOLESTEROL ACYLTRANSFERASE SECRETION INDEPENDENTLY OF EFFECTS ON TRIGLYCERIDE SECRETION IN PRIMARY RAT HEPATOCYTES

The regulation of plasma lecithin:cholesterol acyltransferase (LCAT) e xpression is not well understood. Although oleic acid increases both t he secretion of triglycerides and LCAT by primary rat hepatocytes, the effect of other fatty acids (FA) on LCAT secretion is not known. This study was designed to examine the effect of FA on the hepatic secreti on of LCAT, triglyceride and apolipoprotein A-1 (apoA-1), Primary rat hepatocytes were incubated with serum-free medium, supplemented with i ndividual FA (0-1 mmol/L) for 22-24 h, Preliminary studies indicated a linear secretion of LCAT up to 24 h in both control and FA-treated ce lls. When hepatocytes were incubated with 1 mmol/L FA, the LCAT secret ion increased 50-100% (P < 0.01) in the presence of the 18-carbon FA ( stearic, oleic, elaidic and linoleic acids), whereas the presence of b utyric, lauric and palmitic acids had no significant effect. LCAT secr etion decreased (P < 0.01) in the presence of docosahexaenoic acid (DH A). All FA (except DHA) significantly enhanced triglyceride secretion; however, only the 18 carbon FA significantly stimulated the synthesis and secretion of apoA-1 and secretion of LCAT, The secretion of LCAT correlated with apoA-1 secretion (r = 0.88, P = 0.004) but not with tr iglyceride secretion (r = 0.55, P = 0.12). Treatment with oleic acid r esulted in a 1.5-fold increase in hepatocyte LCAT mRNA accumulation, w hereas butyrate and palmitate had no effect. These data indicate that FA that promote the apparent synthesis and secretion of apoA-1 also st imulate the secretion of LCAT in vitro, suggesting a coordinate regula tory mechanism for apoA-1 and LCAT expression.