Diabetes Metab J.  2013 Aug;37(4):240-248. 10.4093/dmj.2013.37.4.240.

Intestinal and Hepatic Niemann-Pick C1-Like 1

• Park SW

• KMID: 2174264
• DOI: http://doi.org/10.4093/dmj.2013.37.4.240

Abstract

Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1) is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, diabetes, and atherosclerosis. In this review, the identification and characterization of NPC1L1, NPC1L1-dependent cholesterol transport, the relationship with pathogenesis of metabolic disease and its newly introduced function for virus entry are discussed.

Keyword

Cholesterol; Intestines; Liver, Niemann-Pick C1-Like 1

MeSH Terms

Absorption
Atherosclerosis
Azetidines
Cholesterol
Enterocytes
Fatty Liver
Hepatocytes
Hypercholesterolemia
Intestines
Membranes
Metabolic Diseases
Obesity
Ezetimibe
Virus Internalization
Azetidines
Cholesterol

Figure

• 

  Fig. 1 The role of Niemann-Pick C1-Like 1 (NPC1L1) in cholesterol transport in the intestine and liver. NPC1L1 is located at intestinal brush border and hepatocanicular membrane. In the lumen of small intestine, biliary and dietary cholesterol are mixed and solubilized to form micelles. NPC1L1 transports sterols from brush border membrane to intracellular compartments. Most free cholesterol (FC) is esterified by acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2) to form cholesterol esters (CE), packed into chylomicrons and then secreted into mesenteric lymph. Liver NPC1L1 facilitates the transfer of secreted biliary cholesterol back into hepatocytes and prevents cholesterol loss. The cholesterol efflux transporter, ATP-binding cassette transporter G5 and G8 (ABCG5/ABCG8) also localizes at apical membrane of hepatocytes. Ezetimibe inhibits NPC1L1-meidated cholesterol transport in intestine and liver.

Reference

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