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

121 Citations (Scopus)

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

Fingerprint

Cholesterol
Liver
Proteins
Intestinal Absorption
Anticholesteremic Agents
Membranes
Enterocytes
Metabolic Diseases
Sterols
Hypercholesterolemia
Hepatocytes
Homeostasis
Cardiovascular Diseases
Obesity
Diet
Ezetimibe
Hepatobiliary Elimination

Keywords

  • ezetimibe
  • fat absorption
  • hepatic steatosis
  • obesity

ASJC Scopus subject areas

  • Physiology

Cite this

Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. / Jia, Lin; Betters, Jenna L.; Yu, Liqing.

In: Annual Review of Physiology, Vol. 73, 24.02.2011, p. 239-259.

Research output: Contribution to journalArticle

@article{0038ad158080473ea8bc8ab9d3dc6d3f,
title = "Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport",
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.",
keywords = "ezetimibe, fat absorption, hepatic steatosis, obesity",
author = "Lin Jia and Betters, {Jenna L.} and Liqing Yu",
year = "2011",
month = "2",
day = "24",
doi = "10.1146/annurev-physiol-012110-142233",
language = "English (US)",
volume = "73",
pages = "239--259",
journal = "Annual Review of Physiology",
issn = "0066-4278",
publisher = "Annual Reviews Inc.",

}

TY - JOUR

T1 - Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport

AU - Jia, Lin

AU - Betters, Jenna L.

AU - Yu, Liqing

PY - 2011/2/24

Y1 - 2011/2/24

N2 - 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.

AB - 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.

KW - ezetimibe

KW - fat absorption

KW - hepatic steatosis

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=79951793527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951793527&partnerID=8YFLogxK

U2 - 10.1146/annurev-physiol-012110-142233

DO - 10.1146/annurev-physiol-012110-142233

M3 - Article

VL - 73

SP - 239

EP - 259

JO - Annual Review of Physiology

JF - Annual Review of Physiology

SN - 0066-4278

ER -