Bile acid synthesis by cultured rabbit hepatocytes: stimulation by three lipoprotein fractions

Bile acid and cholesterol synthesis were measured in monolayer cultures of rabbit hepatocytes maintained in a defined culture medium. In the absence of lipoproteins, bile acid synthesis and secretion were correlated with cholesterol synthesis and were increased 245% by mevalonolactone (10 mM) and inhibited 45% by lovastatin (50 micrograms/ml) over 24 h. When included in the culture medium, normal rabbit plasma low-density and high-density lipoproteins increased bile acid synthesis and secretion by up to 140% of values obtained without lipoproteins in hepatocytes from normal or cholestyramine-fed rabbits. Three cholesterol-rich lipoprotein fractions (beta-very low density, low density and high density) also were isolated from rabbits fed 1% cholesterol for 14 days. When added to rabbit hepatocyte cultures, each fraction markedly increased hepatocellular cholesterol content, stimulated bile acid synthesis and secretion in a dose-dependent manner, and inhibited cholesterol synthesis from radioactive acetate. These data indicate that three different lipoprotein fractions can provide cholesterol for uptake and subsequent breakdown to bile acids by cultured rabbit hepatocytes.