ArticleJournal of lipid research2012
Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 60 citations in OpenAlex.
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation.Frontiers in pharmacology · 2024Article
- Intestinal Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLRLipids in health and disease · 2021Article
- Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance.Journal of animal science and biotechnology · 2020Review
- Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Ontogenesis and Modulation of Intestinal Unesterified Cholesterol Sequestration in a Mouse Model of Niemann-Pick C1 Disease.Digestive diseases and sciences · 2020Article
- Intestine-Specific Overexpression of LDLR Enhances Cholesterol Excretion and Induces Metabolic Changes in Male Mice.Endocrinology · 2019Article
- Review
- Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model.American journal of physiology. Endocrinology and metabolism · 2019Article
- Developmental and extrahepatic physiological functions of SREBP pathway genes in mice.Seminars in cell & developmental biology · 2018Review
- Effectiveness and safety of combinational therapy compared with intensified statin monotherapy in patients with coronary heart disease.Experimental and therapeutic medicine · 2018Article
- Infant Formula Feeding Increases Hepatic Cholesterol 7α Hydroxylase (CYP7A1) Expression and Fecal Bile Acid Loss in Neonatal Piglets.The Journal of nutrition · 2018Article
- Overactivation of intestinal sterol response element-binding protein 2 promotes diet-induced nonalcoholic steatohepatitis.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Cholesterol auxotrophy and intolerance to ezetimibe in mice with SREBP-2 deficiency in the intestine.Journal of lipid research · 2017Article
- Quantitation of the rates of hepatic and intestinal cholesterol synthesis in lysosomal acid lipase-deficient mice before and during treatment with ezetimibe.Biochemical pharmacology · 2017Article
- The anti-cholesterolaemic effect of a consortium of probiotics: An acute study in C57BL/6J mice.Scientific reports · 2017Article
- Para-bile-osis Establishes a Role for Nonbiliary Macrophage to Feces Reverse Cholesterol Transport.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Review
- Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducingMolecular metabolism · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Enterocyte cholesterol homeostasis reflects aggregated rates of sterol synthesis, efflux, and uptake from plasma and gut lumen. Cholesterol synthesis and LDL uptake are coordinately regulated by sterol regulatory element-binding proteins (SREBP), whereas sterol efflux is regulated by liver X receptors (LXR). How these processes are coordinately regulated in enterocytes, the site of cholesterol absorption, is not well understood. Here, we treat mice with ezetimibe to investigate the effect of blocking cholesterol absorption on intestinal SREBPs, LXRs, and their effectors. Ezetimibe increased nuclear SREBP-2 8-fold. HMG-CoA reductase (HMGR) and LDL receptor (LDLR) mRNA levels increased less than 3-fold, whereas their protein levels increased 30- and 10-fold, respectively. Expression of inducible degrader of LDLR (IDOL), an LXR-regulated gene that degrades LDLRs, was reduced 50% by ezetimibe. Coadministration of ezetimibe with the LXR agonist T0901317 abolished the reduction in IDOL and prevented the increase in LDLR protein. Ezetimibe-stimulated LDLR expression was independent of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. To maintain cholesterol homeostasis in the face of ezetimibe, enterocytes boost LDL uptake by increasing LDLR number, and they boost sterol synthesis by increasing HMGR and other cholesterologenic genes. These studies reveal a hitherto undescribed homeostatic network in enterocytes triggered by blockade of cholesterol absorption.
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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.