REGULATION OF HEPATIC LDL METABOLISM IN THE GUINEA-PIG BY DIETARY-FATAND CHOLESTEROL

Studies were carried out to determine the independent and interactive effects of dietary fat and cholesterol on the regulation of hepatic ap oB/E receptor expression and its relationship to hepatic cholesterol c oncentrations and low density lipoprotein (LDL) particle characteristi cs. Guinea pigs were fed 15% (w/w) fat diets (lard, olive oil, or corn oil) with cholesterol levels corresponding to absorbed intakes of 6 ( basal), 50, 100, or 200% endogenous cholesterol synthesis. Guinea pigs main tained stable plasma cholesterol levels until cholesterol intake equaled or exceeded endogenous synthesis (P < 0.001). Fat type indepe ndently affected plasma total and LDL cholesterol levels such that lar d > corn oil, with olive oil being intermediate (P < 0.05). Hepatic me mbrane apoB/E receptor number (B-max) decreased as dietary cholesterol increased (P < 0.001) without an independent effect of dietary fat sa turation. B-max values were significantly correlated with plasma LDL c holesterol levels (r = -0.632), and with hepatic free (r = 0.527) and esterified cholesterol (r = -0.512) concentrations, which were both in creased with dietary cholesterol(P < 0.001). Significant interactions between dietary fat type and cholesterol mediated the extent of hepati c free and esterified cholesterol accumulation. Dietary fat and choles terol interactions also contributed to changes in LDL particle composi tion and peak density. The results of these studies do not support the thesis that dietary cholesterol-mediated suppression of apoB/E recept or expression is ameliorated by intake of polyunsaturated fatty acids. Dietary fat type and cholesterol amount interactively affect hepatic cholesterol concentrations and LDL composition and size, which in part determine plasma LDL cholesterol levels.