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. 2004 Feb 20;303(5661):1201-4.
doi: 10.1126/science.1093131.

Niemann-Pick C1 Like 1 Protein Is Critical for Intestinal Cholesterol Absorption

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Niemann-Pick C1 Like 1 Protein Is Critical for Intestinal Cholesterol Absorption

Scott W Altmann et al. Science. .

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 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.

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