Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport

Annu Rev Physiol. 2011;73:239-59. doi: 10.1146/annurev-physiol-012110-142233.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism
  • Azetidines / pharmacology
  • Biliary Tract / drug effects
  • Biliary Tract / metabolism
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Carrier Proteins / metabolism*
  • Cholesterol / metabolism*
  • Endocytosis / drug effects
  • Endocytosis / physiology
  • Ezetimibe
  • Fatty Liver / drug therapy
  • Fatty Liver / metabolism
  • Humans
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Liver / drug effects
  • Liver / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins
  • Mice
  • Obesity / drug therapy
  • Obesity / metabolism
  • Phytosterols / metabolism
  • Primates / metabolism

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Carrier Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • NPC1L1 protein, human
  • Phytosterols
  • Cholesterol
  • Ezetimibe