2004
DOI: 10.1074/jbc.m405817200
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Niemann-Pick C1 Like 1 (NPC1L1) Is the Intestinal Phytosterol and Cholesterol Transporter and a Key Modulator of Whole-body Cholesterol Homeostasis

Abstract: Niemann-Pick C1 Like 1 (NPC1L1) is a protein localized in jejunal enterocytes that is critical for intestinal cholesterol absorption. The uptake of intestinal phytosterols and cholesterol into absorptive enterocytes in the intestine is not fully defined on a molecular level, and the role of NPC1L1 in maintaining whole body cholesterol homeostasis is not known. NPC1L1 null mice had substantially reduced intestinal uptake of cholesterol and sitosterol, with dramatically reduced plasma phytosterol levels. The NPC… Show more

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Cited by 636 publications
(515 citation statements)
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“…In the present study there was a close correlation between ABCG5 and ABCG8 mRNA in both diabetic and control subjects (Fig. 3), which was expected since these proteins are known to work in tandem to expel cholesterol from the enterocyte [18]. Diabetic patients had significantly lower ABCG5 and ABCG8 mRNA expression, suggesting they have an impairment in the re-excretion of cholesterol from the enterocyte back into the lumen.…”
Section: Discussionsupporting
confidence: 73%
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“…In the present study there was a close correlation between ABCG5 and ABCG8 mRNA in both diabetic and control subjects (Fig. 3), which was expected since these proteins are known to work in tandem to expel cholesterol from the enterocyte [18]. Diabetic patients had significantly lower ABCG5 and ABCG8 mRNA expression, suggesting they have an impairment in the re-excretion of cholesterol from the enterocyte back into the lumen.…”
Section: Discussionsupporting
confidence: 73%
“…We had expected that inhibition of cholesterol synthesis would increase NPC1L1 mRNA, since NPC1L1 deficiency results in upregulation of HMGCoA reductase. It has recently been shown that NPC1L1 null mice had increased HMGCoA synthase expression [18]. In acute experiments, inhibition of NPC1L1 by ezetimibe does not affect acute intestinal or hepatic cholesterol synthesis in rats [34], but we are unaware of any other studies on the relationship between HMGCoA reductase inhibition and NPC1L1 mRNA.…”
Section: Discussionmentioning
confidence: 89%
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“…The present study did not show a significant effect of cholesterol on these two genes in the small intestine in hamsters. Some studies in mice have shown that dietary supplementation of cholesterol increases the expression of ABCG5 and ABCG8 in the small intestine 18,32,33,35 while others did not show any effect 25,36 . Studies in hamsters 23 and rats 34 did not show any effect of dietary cholesterol on ABCG5 and ABCG8 expressions in the small intestine.…”
Section: Discussionmentioning
confidence: 99%