ArticleBiochimica et biophysica acta2011
Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann-Pick C1-Like 1 only in liver.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- Ezetimibe in Combination With Simvastatin Reduces Remnant Cholesterol Without Affecting Biliary Lipid Concentrations in Gallstone Patients.Journal of the American Heart Association · 2018Trial
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Response0 surface guided design of lipid-polymer hybrid nanoparticles for dual delivery of rosuvastatin and ezetimibe.Discover nano · 2026Article
- The Hypocholesterolemic Potential of the Edible AlgaeFoods (Basel, Switzerland) · 2023Article
- The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Pathophysiological importance of bile cholesterol reabsorption: hepatic NPC1L1-exacerbated steatosis and decreasing VLDL-TG secretion in mice fed a high-fat diet.Lipids in health and disease · 2019Article
- Computational Modeling Explains the Multi Sterol Ligand Specificity of the N-Terminal Domain of Niemann-Pick C1-Like 1 Protein.ACS omega · 2019Article
- Hepatic NPC1L1 overexpression attenuates alcoholic autophagy in mice.Molecular medicine reports · 2019Article
- Effects of Saponin from Trigonella Foenum-Graecum Seeds on Dyslipidemia.Iranian journal of medical sciences · 2017Article
- Osteopontin deficiency protects mice from cholesterol gallstone formation by reducing expression of intestinal NPC1L1.Molecular medicine reports · 2017Article
- The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.PloS one · 2016Article
- Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.Advances in nutrition (Bethesda, Md.) · 2015Review
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- Ezetimibe inhibits hepatic Niemann-Pick C1-Like 1 to facilitate macrophage reverse cholesterol transport in mice.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Niemann-Pick C1-Like 1 (NPC1L1) is highly expressed in the small intestine across mammalian species and is the target of ezetimibe, a potent cholesterol absorption inhibitor. In humans, NPC1L1 is also expressed in the liver. We found that transgenic overexpression of NPC1L1 in the wild-type mouse liver inhibits biliary cholesterol secretion and raises blood cholesterol, which can be reversed by ezetimibe treatment. Unfortunately, the high expression of endogenous NPC1L1 in the intestine hampered a definitive establishment of the role of hepatic NPC1L1 in cholesterol metabolism and ezetimibe action in the liver because intestinal NPC1L1 dramatically influences cholesterol homeostasis and is a target of ezetimibe. To circumvent this obstacle, we crossed liver-specific NPC1L1 transgenic mice to NPC1L1 knockout (L1-KO) mice and created a mouse line expressing no endogenous NPC1L1, but human NPC1L1 in liver only (L1(LivOnly) mice). Compared to L1-KO mice, L1(LivOnly) mice on a 0.2% cholesterol diet showed significantly increased hepatic and plasma cholesterol, and despite a 90% reduction in biliary cholesterol excretion, their fecal cholesterol excretion remained completely unaltered. Remarkably, 4days of ezetimibe treatment significantly restored biliary cholesterol secretion in L1(LivOnly) mice. These findings demonstrated a direct role of hepatic NPC1L1 in regulating biliary cholesterol excretion and hepatic/blood cholesterol levels, and unequivocally established hepatic NPC1L1 as a target of ezetimibe.
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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.