title: Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport.
abstract: Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counter-balances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases.
authors.affiliation: Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Betters
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D001384:Azetidines / Q000494:pharmacology; D001659:Biliary Tract / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D000069438:Ezetimibe; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010840:Phytosterols / Q000378:metabolism; D011323:Primates / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010840:Phytosterols; D002784:Cholesterol; D000069438:Ezetimibe
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