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Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.

Dietary cholesterol consumption and intestinal cholesterol absorption contribute to plasma cholesterol levels, a risk factor for coronary heart disease. The molecular mechanism of sterol uptake from the lumen of the small intestine is poorly defined. We show that Niemann-Pick C1 Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol. NPC1L1 expression is enriched in the small intestine and is in the brush border membrane of enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice exhibit a substantial reduction in absorbed cholesterol, which is unaffected by dietary supplementation of bile acids. Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.

Pubmed ID: 14976318

Authors

  • Altmann SW
  • Davis HR
  • Zhu LJ
  • Yao X
  • Hoos LM
  • Tetzloff G
  • Iyer SP
  • Maguire M
  • Golovko A
  • Zeng M
  • Wang L
  • Murgolo N
  • Graziano MP

Journal

Science (New York, N.Y.)

Publication Data

February 20, 2004

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Anticholesteremic Agents
  • Azetidines
  • Cholesterol
  • Cholesterol, Dietary
  • Cholic Acid
  • Computational Biology
  • Enterocytes
  • Female
  • Gene Expression Profiling
  • Humans
  • Intestinal Absorption
  • Intestine, Small
  • Jejunum
  • Liver
  • Male
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Proteins
  • Rats
  • Rats, Sprague-Dawley