title: Citrus pectin and cholesterol interact to regulate hepatic cholesterol homeostasis and lipoprotein metabolism: a dose-response study in guinea pigs.
abstract: 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% and 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 whereas hepatic cholesterol concentrations and acyl-CoA:cholesterol acyltransferase (ACAT) activity were not different. In contrast, with HC diets, plasma LDL concentrations were reduced in a dose-response manner by 29%, 30%, and 67% with 7.5%, 10%, and 12.5% CP intake (P < 0.001) and apolipoprotein B/E receptor number was increased and inversely correlated 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. Hepatic HMG-CoA reductase activity was suppressed by HC diets and only intake of 12.5% CP reversed this suppression. The most significant effects of CP on hepatic cholesterol, enzymes of hepatic cholesterol homeostasis, and the apolipoprotein B/E receptor were in animals fed the HC diets. These metabolic alterations partially explain the reduced plasma LDL of guinea pigs fed large amounts of CP.
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson 85721.
authors.forename: M L
authors.initials: ML
authors.lastname: Fernandez
authors.forename: D M
authors.initials: DM
authors.lastname: Sun
authors.forename: M A
authors.initials: MA
authors.lastname: Tosca
authors.forename: D J
authors.initials: DJ
authors.lastname: McNamara
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D004043:Dietary Fiber; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006706:Homeostasis / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D010368:Pectins / Q000494:pharmacology*; D018110:Receptors, Lipoprotein / Q000032:analysis; D002785:Sterol O-Acyltransferase / Q000032:analysis
chemical_list: D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D004043:Dietary Fiber; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018110:Receptors, Lipoprotein; C072413:apolipoprotein B receptor; D010368:Pectins; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase