Cholesterol and plant sterol absorption: recent insights.
The recent discovery of transporters in the intestinal mucosa and the canalicular membrane has given new insights into the regulation of intestinal absorption as well as the biliary output of cholesterol and plant sterols. The 2 adenosine triphosphate (ATP)-binding cassette (ABC) half-transporters ABCG5 and ABCG8 are expressed in the mucosa cells and the canalicular membrane, and they resecrete sterols, especially absorbed plant sterols, back into the intestinal lumen and from the liver into bile. Defects of either of these cotransporters lead to the rare inherited disease of phytosterolemia, which is clinically defined by hyperabsorption and diminished biliary excretion of plant sterols. Furthermore, it has been recently demonstrated that the Niemann-Pick C1-Like 1 (NPC1L1) transporter is most likely responsible for the transport of cholesterol and plant sterols from the brush border membrane into the intestinal mucosa. Ezetimibe interferes with NPC1L1, reducing the intestinal uptake of cholesterol and plant sterols. These new findings contribute to our understanding of cholesterol and plant sterol concentrations in serum, and the effect of dietary and drug intervention to reduce serum concentrations of sterols.
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany. Klaus.von_Bergmann@ukb.uni-bonn.de
Klaus
K
von Bergmann
Thomas
T
Sudhop
Dieter
D
Lütjohann
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000042:Absorption; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use; D002784:Cholesterol / Q000493:pharmacokinetics*; D004032:Diet; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins; D008871:Microvilli / Q000502:physiology; D010840:Phytosterols / Q000493:pharmacokinetics; D011506:Proteins / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001384:Azetidines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010840:Phytosterols; D011506:Proteins; D002784:Cholesterol; D000069438:Ezetimibe