CITRUS PECTIN AND CHOLESTEROL INTERACT TO REGULATE HEPATIC CHOLESTEROL HOMEOSTASIS AND LIPOPROTEIN METABOLISM - A DOSE-RESPONSE STUDY IN GUINEA-PIGS

Guinea pigs were fed increasing concentrations of citrus pectin (CP) ( 0-12.5%, wt/wt) with low (LC, 0.04%) or high (HC, 0.25%) cholesterol. Animals fed LC diets had reduced plasma LDL concentrations with 10% an d 12.5% CP and hepatic membrane apolipoprotein B/E receptor expression increased with high dosages of CP. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased with 12.5% CP where as hepatic cholesterol concentrations and acyl-CoA: cholesterol acyltr ansferase (ACAT) activity were not different. In contrast, with HC die ts, plasma LDL concentrations were reduced in a dose-response manner b y 29%, 30%, and 67% with 7.5%, 10%, and 12.5% CP intake (P < 0.001) an d apolipoprotein B/E receptor number was increased and inversely corre lated with plasma LDL in the HC group (r = -0.81, P < 0.005). Animals fed HC diets had a dose-dependent decrease in hepatic cholesterol and ACAT activity, with intake of 12.5% CP having the major effect. Hepati c HMG-CoA reductase activity was suppressed by HC diets and only intak e of 12.5% CP reversed this suppression. The most significant effects of CP on hepatic cholesterol, enzymes of hepatic cholesterol homeostas is, and the apolipoprotein B/E receptor were in animals fed the HC die ts. These metabolic alterations partially explain the reduced plasma L DL of guinea pigs fed large amounts of CP.