Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption |
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| Authors: | Altmann Scott W Davis Harry R Zhu Li-Ji Yao Xiaorui Hoos Lizbeth M Tetzloff Glen Iyer Sai Prasad N Maguire Maureen Golovko Andrei Zeng Ming Wang Luquan Murgolo Nicholas Graziano Michael P |
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| Institution: | Department of Cardiovascular/Endocrine Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ, 07033-0539, USA. scott.altmann@spcorp.com |
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| 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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