New insights into the genetic regulation of intestinal cholesterol absorption.

  • F. L
  • Lammert F
  • Wang D
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Abstract

The small intestine is a unique organ providing dietary and reabsorbed biliary cholesterol to the body. However, the molecular mechanisms whereby cholesterol is absorbed have not yet been fully understood. Recent research suggests that the newly identified Niemann-Pick C1-like 1 protein (NPC1L1) is expressed at the apical surface of enterocytes and plays a critical role in the absorption of intestinal cholesterol. Furthermore, adenosine triphosphate (ATP)-binding cassette (ABC) transporters ABCG5 and ABCG8 represent apical sterol export pumps that promote active efflux of cholesterol and plant sterols from enterocytes back into the intestinal lumen for excretion. This provides an explanation why cholesterol absorption is a selective process, with plant sterols and other noncholesterol sterols being absorbed poorly or not at all. These findings strongly support the concept that cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. The absorption efficiency of cholesterol is most likely determined by the net effect between influx and efflux of intraluminal cholesterol molecules across the brush border of the enterocyte. Combination therapy using a novel, specific, and potent cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and HMG-CoA reductase inhibitors (statins) offers an efficacious new approach to the prevention and treatment of hypercholesterolemia. © 2005 by the American Gastroenterological Association.

Author-supplied keywords

  • *Cholesterol/me [Metabolism]
  • *Hypercholesterolemia/ge [Genetics]
  • *Hypercholesterolemia/pp [Physiopathology]
  • *Intestinal Absorption/ge [Genetics]
  • *Membrane Transport Proteins/ge [Genetics]
  • *cholesterol
  • *genetic regulation
  • *lipid absorption
  • *small intestine absorption
  • ABC transporter A1/ec [Endogenous Compound]
  • ABC transporter/ec [Endogenous Compound]
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Intestinal Absorption/ph [Physiology]
  • Intestine
  • Male
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Small
  • abnormally high substrate concentration in blood/s
  • acid/pd [Pharmacology]
  • aminotransferase blood level
  • aminotransferase/ec [Endogenous Compound]
  • atorvastatin/ae [Adverse Drug Reaction]
  • atorvastatin/cb [Drug Combination]
  • atorvastatin/dt [Drug Therapy]
  • atp binding cassette transporter g5/ec [Endogenous
  • atp binding cassette transporter g8/ec [Endogenous
  • beta muricholic acid/pd [Pharmacology]
  • bile acid
  • cell surface
  • cholesterol acyltransferase inhibitor/ct [Clinical
  • cholesterol acyltransferase inhibitor/pd [Pharmaco
  • cholesterol ester transfer protein inhibitor/ct [C
  • cholesterol intake
  • cholesterol stone/dt [Drug Therapy]
  • cholesterol transport
  • cholic acid/pd [Pharmacology]
  • clinical trial
  • colestipol/pd [Pharmacology]
  • colestyramine/pd [Pharmacology]
  • drug mechanism
  • enzyme activity
  • excretion
  • ezetimibe/ae [Adverse Drug Reaction]
  • ezetimibe/cb [Drug Combination]
  • ezetimibe/dt [Drug Therapy]
  • ezetimibe/pd [Pharmacology]
  • gamma glutamyl transferase blood level
  • gamma glutamyltransferase/ec [Endogenous Compound]
  • gene activity
  • gene expression regulation
  • genetic code
  • genetic variability
  • glucuronide/cm [Drug Comparison]
  • glucuronide/pd [Pharmacology]
  • glucuronide/po [Oral Drug Administration]
  • heredity
  • human
  • hydroxymethylglutaryl coenzyme A reductase inhibit
  • hypercholesterolemia/dt [Drug Therapy]
  • hypercholesterolemia/pc [Prevention]
  • intestine brush border
  • intestine cell
  • intestine transit time
  • molecular dynamics
  • niemann pick c1 like 1 protein/ec [Endogenous Comp
  • nonhuman
  • phytosterol/pd [Pharmacology]
  • priority journal
  • protein analysis
  • protein expression
  • protein function
  • protein/ec [Endogenous Compound]
  • quantitative trait locus
  • resin/pd [Pharmacology]
  • review
  • scavenger receptor BI/ec [Endogenous Compound]
  • sch 60663/pd [Pharmacology]
  • sch 60663/po [Oral Drug Administration]
  • sex difference
  • simvastatin/ae [Adverse Drug Reaction]
  • simvastatin/cb [Drug Combination]
  • simvastatin/dt [Drug Therapy]
  • small intestine
  • stigmasterol/pd [Pharmacology]
  • tetrahydrolipstatin/pd [Pharmacology]
  • unclassified drug
  • ursodeoxycholic acid/ct [Clinical Trial]
  • ursodeoxycholic acid/dt [Drug Therapy]
  • ursodeoxycholic acid/pd [Pharmacology]

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Authors

  • Lammert F.

  • Frank Lammert

  • David Q-H Wang

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