Dietary cholesterol does not normalize low plasma cholesterol levels but induces hyperbilirubinemia and hypercholanemia in Mdr2 P-glycoprotein-deficient mice
article
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
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
Topics
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
TNO Identifier
235998
ISSN
01688278
Source
Journal of Hepatology, 34(2), pp. 202-209.
Pages
202-209
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