Print Email Facebook Twitter Dietary cholesterol does not normalize low plasma cholesterol levels but induces hyperbilirubinemia and hypercholanemia in Mdr2 P-glycoprotein-deficient mice Title Dietary cholesterol does not normalize low plasma cholesterol levels but induces hyperbilirubinemia and hypercholanemia in Mdr2 P-glycoprotein-deficient mice Author Voshol, P.J. Koopen, N.R. de Vree, J.M.L. Havinga, R. Princen, H.M.G. Oude Elferink, R.P.J Groen, A.K. Kuipers, F. Gaubius Instituut TNO Publication year 2001 Abstract Background/Aims: Mdr2 P-glycoprotein deficiency in mice (Mdr2(-/-)) leads to formation of cholesterol/cholesterol-depleted bile and reduced plasma HDL cholesterol. We addressed the questions: (1) does HDL in Mdr2(-/-) mice normalize upon phospholipid and/or cholesterol feeding, and (2): is the Mdr2(-/-) liver capable of handling excess dietary cholesterol. Methods: Male and female Mdr2(-/-) and Mdr2(+/+) mice were fed diets with or without additional phosphatidylcholine and/or cholesterol. Plasma, hepatic and biliary lipids as well as liver function parameters and expression of transport proteins involved in bile formation were analyzed. Results: Feeding excess phospholipids and/or cholesterol did not affect lipoprotein levels in Mdr2(+/+) or Mdr2(-/+) mice. Dietary cholesterol caused hyperbilirubinemia (male +100%; female +500%) and elevated plasma bile salts (male + 200%; female + 1250,%) in Mdr2(-/-) mice only, independent of phospholipids. Bile flow nor biliary bile salt and bilirubin secretion were affected in cholesterol-fed Mdr2(-/-) mice. Elevated plasma bile salts may be related to cholesterol-induced reduction of hepatic Na+-taurocholate cotransporting protein expression in Mdr2(-/-) mice. Conclusion: Excess dietary phospholipids and cholesterol do not normalize low HDL associated with Mdr2 P-glycoprotein-deficiency. Induction of hyperbilirubinemia and hypercholanemia by dietary cholesterol in Mdr2(-/-) mice delineates the important role of biliary lipid secretion in normal hepatic functioning. © 2001 European Association for the Study of the Liver. Chemicals/CAS: Antigens, CD36; ATP-Binding Cassette Transporters; Bile Acids and Salts; Carrier Proteins; Cholesterol, 57-88-5; Cholesterol, Dietary; DNA Primers; Membrane Proteins; Membrane Transport Proteins; multidrug resistance protein 3; Organic Anion Transporters, Sodium-Dependent; P-Glycoproteins; Receptors, Immunologic; Receptors, Lipoprotein; Receptors, Scavenger; RNA, Messenger; Scarb1 protein, mouse; Scavenger Receptors, Class B; sodium-bile acid cotransporter, 145420-23-1; Symporters Subject AnimalsAntigens, CD36ATP-Binding Cassette TransportersBase SequenceBileBile Acids and SaltsCarrier ProteinsCholesterolCholesterol, DietaryDNA PrimersFemaleGene ExpressionHyperbilirubinemiaLiverMaleMembrane ProteinsMembrane Transport ProteinsMiceMice, KnockoutOrganic Anion Transporters, Sodium-DependentP-GlycoproteinsReceptors, ImmunologicReceptors, LipoproteinReceptors, ScavengerRNA, MessengerScavenger Receptors, Class BSymporters To reference this document use: http://resolver.tudelft.nl/uuid:69193c6f-9b88-48ca-83c4-c49cfef35009 DOI https://doi.org/10.1016/s0168-8278(00)00021-0 TNO identifier 235998 ISSN 0168-8278 Source Journal of Hepatology, 34 (2), 202-209 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.