ArticleJournal of lipid research2010
Niemann-Pick C1-Like 1 deletion in mice prevents high-fat diet-induced fatty liver by reducing lipogenesis.
Article in Journal of lipid research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial.Diabetologia · 2014Trial
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- Dietary curcumin prevents hypercholesterolemia by inhibiting the transcriptional activity of SREBP-2 and HNF1α and reducing intestinal and hepatic NPC1L1 expression in high-fat diet-fed hamsters.Nutrition & metabolism · 2025Article
- Identification of a Novel NPC1L1 Inhibitor from Danshen and Its Role in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2025Article
- Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane.Gastroenterology report · 2025Review
- X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction.Nature communications · 2024Article
- Ezetimibe and Cancer: Is There a Connection?Frontiers in pharmacology · 2022Review
- Article
- Transcriptomic Responses in the Livers and Jejunal Mucosa of Pigs under Different Feeding Frequencies.Animals : an open access journal from MDPI · 2019Article
- Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin.Scientific reports · 2018Article
- Exacerbating and reversing lysosomal storage diseases: from yeast to humans.Microbial cell (Graz, Austria) · 2017Review
- Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease: The Potential Role of Ezetimibe.Digestive diseases and sciences · 2016Review
- Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.Biochimica et biophysica acta · 2016Article
- Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.PloS one · 2016Article
- Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats.World journal of gastroenterology · 2015Article
- Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.Scientific reports · 2015Article
- Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes muscle steatosis but improves insulin sensitivity in male mice.Endocrinology · 2015Article
- Article
- Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation.Nature communications · 2014Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal absorption of dietary and biliary cholesterol. Ezetimibe, by inhibiting NPC1L1 function, is widely used to treat hypercholesterolemia in humans. Interestingly, ezetimibe treatment appears to attenuate hepatic steatosis in rodents and humans without a defined mechanism. Over-consumption of a high-fat diet (HFD) represents a major cause of metabolic disorders including fatty liver. To determine whether and how NPC1L1 deficiency prevents HFD-induced hepatic steatosis, in this study, we fed NPC1L1 knockout (L1-KO) mice and their wild-type (WT) controls an HFD, and found that 24 weeks of HFD feeding causes no fatty liver in L1-KO mice. Hepatic fatty acid synthesis and levels of mRNAs for lipogenic genes are substantially reduced but hepatic lipoprotein-triglyceride production, fatty acid oxidation, and triglyceride hydrolysis remain unaltered in L1-KO versus WT mice. Strikingly, L1-KO mice are completely protected against HFD-induced hyperinsulinemia under both fed and fasted states and during glucose challenge. Despite similar glucose tolerance, L1-KO relative WT mice are more insulin sensitive and in the overnight-fasted state display significantly lower plasma glucose concentrations. In conclusion, NPC1L1 deficiency in mice prevents HFD-induced fatty liver by reducing hepatic lipogenesis, at least in part, through attenuating HFD-induced insulin resistance, a state known to drive hepatic lipogenesis through elevated circulating insulin levels.
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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 Socratic graph.