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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Anticholesteremic Agents / pharmacology
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Atherosclerosis / drug therapy
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Atherosclerosis / metabolism
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Azetidines / pharmacology
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Biliary Tract / drug effects
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Biliary Tract / metabolism
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Biological Transport / drug effects
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Biological Transport / physiology
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Carrier Proteins / metabolism*
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Cholesterol / metabolism*
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Endocytosis / drug effects
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Endocytosis / physiology
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Ezetimibe
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Fatty Liver / drug therapy
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Fatty Liver / metabolism
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Humans
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Intestinal Absorption / drug effects
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Intestinal Absorption / physiology
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Intestinal Mucosa / metabolism*
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Intestines / drug effects
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Liver / drug effects
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Liver / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Transport Proteins
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Mice
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Obesity / drug therapy
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Obesity / metabolism
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Phytosterols / metabolism
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Primates / metabolism
Substances
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Anticholesteremic Agents
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Azetidines
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Carrier Proteins
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Membrane Proteins
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Membrane Transport Proteins
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NPC1L1 protein, human
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Phytosterols
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Cholesterol
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Ezetimibe