BILE-ACID AND VERY-LOW-DENSITY LIPOPROTEIN PRODUCTION BY CULTURED-HEPATOCYTES FROM HYPORESPONSIVE OR HYPERRESPONSIVE RABBITS FED CHOLESTEROL

Two groups of rabbits, either hyperresponsive or hyporesponsive to die tary cholesterol, were selected after ten weeks of cholesterol feeding (0.2 g cholesterol/kg body weight per day). Bile acids and very low d ensity lipoprotein (VLDL) production were determined in primary hepato cyte cultures from control, hyper- and hyporesponsive rabbits. Free ch olesterol and cholesteryl ester contents in hepatocytes of the hyperre sponsive rabbits was significantly increased. In contrast, lipid compo sition in hepatocytes of the hyporesponders was similar to that of con trol cells. Cholic acid was the predominant bile acid in the culture m edium of hepatocytes together with small amounts of chenodeoxycholic a nd deoxycholic acids. The rate of cholic acid production by hepatocyte s in the hyporesponsive group was two times higher than that in the hy perresponsive group. Bile acid production by control hepatocytes was s lightly higher than in the hyperresponsive group. In contrast, secreti on of VLDL cholesteryl ester was significantly increased by hepatocyte s of the hyperresponsive rabbits. Similar differences in bile acid pro duction were found between hypo- and hyperresponsive rabbits selected after five days of cholesterol feeding and subsequent maintenance on a low cholesterol diet for a period of one month. The results suggest t hat the increased rate of bile acid production could contribute to the apparent resistance of hyporesponders to the atherogenic diet.