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 RIS Download
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