Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport

Lin Jia, Jenna L. Betters, Liqing Yu

Research output: Contribution to journalArticle

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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 counterbalances 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.

Original languageEnglish (US)
Pages (from-to)239-259
Number of pages21
JournalAnnual review of physiology
Volume73
DOIs
StatePublished - Feb 24 2011

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Keywords

  • ezetimibe
  • fat absorption
  • hepatic steatosis
  • obesity

ASJC Scopus subject areas

  • Physiology

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