Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption
Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption
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DOI：
10.1126/science.1093131
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发表时间：
2004-02-20
期刊：
影响因子：
56.9
通讯作者：
Graziano, MP
中科院分区：
文献类型：
--
作者：
Altmann, SW;Davis, HR;Graziano, MP
饮食胆固醇消耗和肠道胆固醇吸收有助于血浆胆固醇水平，这是冠心病的危险因素。从小肠腔中摄取甾醇的分子机制尚不清楚。我们发现，尼曼-皮克C1样1（NPC 1 L1）蛋白在肠道胆固醇的吸收中起着关键作用。NPC 1 L1表达在小肠中富集，并且在肠细胞的刷状缘膜中。尽管在其他方面表型正常，但NPC 1 L1缺陷小鼠表现出吸收的胆固醇显著减少，这不受胆汁酸饮食补充的影响。依折麦布是一种抑制胆固醇吸收的药物，在NPC 1 L1基因敲除小鼠中没有作用，表明NPC 1 L1存在于负责肠道胆固醇吸收的依折麦布敏感途径中。
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.