Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.
Journal:
Science 2004 FebAuthors:
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
Abstract
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 phenot
...[more]ypically 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.[less]
Mesh Headings:
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