ArticleAtherosclerosis2014
Genetic demonstration of intestinal NPC1L1 as a major determinant of hepatic cholesterol and blood atherogenic lipoprotein levels.
Article in Atherosclerosis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.Science (New York, N.Y.) · 2023Article
- Fluorescent visualization and evaluation of NPC1L1-mediated vesicular endocytosis during intestinal cholesterol absorption in mice.Life metabolism · 2023Article
- Article
- Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers.Biomolecules · 2021Review
- NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells.American journal of physiology. Cell physiology · 2021Article
- Efficacy of Polyphenols in the Management of Dyslipidemia: A Focus on Clinical Studies.Nutrients · 2021Review
- Brown Algae Potential as a Functional Food against Hypercholesterolemia: Review.Foods (Basel, Switzerland) · 2021Review
- Mechanisms and regulation of cholesterol homeostasis.Nature reviews. Molecular cell biology · 2020Review
- Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducingMolecular metabolism · 2016Article
- Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe correlation between intestinal cholesterol absorption values and plasma low-density lipoprotein-cholesterol (LDL-C) levels remains controversial. Niemann-Pick-C1-Like 1 (NPC1L1) is essential for intestinal cholesterol absorption, and is the target of ezetimibe, a cholesterol absorption inhibitor. However, studies with NPC1L1 knockout mice or ezetimibe cannot definitively clarify this correlation because NPC1L1 expression is not restricted to intestine in humans and mice. In this study we sought to genetically address this issue. METHODS AND
resultsWe developed a mouse model that lacks endogenous (NPC1L1) and LDL receptor (LDLR) (DKO), but transgenically expresses human NPC1L1 in gastrointestinal tract only (DKO/L1(IntOnly) mice). Our novel model eliminated potential effects of non-intestinal NPC1L1 on cholesterol homeostasis. We found that human NPC1L1 was localized at the intestinal brush border membrane of DKO/L1(IntOnly) mice. Cholesterol feeding induced formation of NPC1L1-positive vesicles beneath this membrane in an ezetimibe-sensitive manner. Compared to DKO mice, DKO/L1(IntOnly) mice showed significant increases in cholesterol absorption and blood/hepatic/biliary cholesterol. Increased blood cholesterol was restricted to very low-density lipoprotein (VLDL) and LDL fractions, which was associated with increased secretion and plasma levels of apolipoproteins B100 and B48. Additionally, DKO/L1(IntOnly) mice displayed decreased fecal cholesterol excretion and hepatic/intestinal expression of cholesterologenic genes. Ezetimibe treatment virtually reversed all of the transgene-related phenotypes in DKO/L1(IntOnly) mice.
conclusionOur findings from DKO/L1(IntOnly) mice clearly demonstrate that NPC1L1-mediated cholesterol absorption is a major determinant of blood levels of apolipoprotein B-containing atherogenic lipoproteins, at least in mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.