THE EFFECT OF BETA,BETA'-TETRAMETHYLHEXADECANEDIOIC ACID (MEDICA-16) ON PLASMA VERY-LOW-DENSITY LIPOPROTEIN METABOLISM IN RATS - ROLE OF APOLIPOPROTEIN C-III

Short term treatment of rats with beta,beta'-tetramethylhexadecanedioi c acid (MEDICA 16) results in a pronounced decrease in plasma very-low -density-lipoprotein (VLDL) cholesterol and VLDL triacylglycerol, prev iously ascribed to a decrease in liver VLDL production [Bar-Tana, Rose -Kahn, Frenkel, Shafer and Fainaru (1988) J. Lipid Res. 29, 431-441]. The hypolipidaemic effect of MEDICA 16 was further analysed here by mo nitoring plasma VLDL clearance and its hepatic uptake. VLDL triacylgly cerol and VLDL apolipoprotein (apo) B fractional clearance rates were increased 7-8-fold in MEDICA 16-treated rats. The increase in the frac tional clearance rate of plasma VLDL was essentially eliminated by fun ctional hepatectomy. It was accounted for by activation of plasma VLDL uptake by the liver being completed during the first 4 min after the injection of the VLDL label and before commencement of uptake in non-t reated animals. The hypolipidaemic effect of MEDICA 16 was accompanied by a 3.5-fold decrease in plasma apoC-III, but plasma apoC-III cleara nce remained unaffected by MEDICA 16. MEDICA 16-induced premature hepa tic uptake of plasma VLDL due to suppression of apoC-III production ma y thus account for enhancement of plasma VLDL clearance in treated ani mals.