ArticleNature communications2025
A mutation in LXRα uncovers a role for cholesterol sensing in limiting metabolic dysfunction-associated steatohepatitis.
Article in Nature communications, 2025. 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 trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed.
- An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial.Nature medicine · 2026Trial
- Hepatic fibrosis extracellular matrix stiffness induces abnormal maturation of dendritic cell via AMPK inhibition-mediated cholesterol accumulation.Materials today. Bio · 2026Article
- CIDEB and CGI-58 differentially regulate liver lipid-droplet cholesterol to modulate metabolic dysfunction-associated steatohepatitis severity.Cell reports · 2026Article
- Review
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Synergistic Effect of Liraglutide and Strength-Endurance Exercise Training on Hepatic Oxidative Stress and Lipid Metabolism in Middle-Aged Male Rats.Antioxidants (Basel, Switzerland) · 2025Article
- Innovative gene engineering and drug delivery systems for dendritic cells in cancer immunotherapy.Journal of biomedical science · 2025Review
- Lactobacillus rhamnosus B16 regulates lipid metabolism homeostasis by producing acetic acid.Journal of translational medicine · 2025Article
- G-protein-coupled receptor ADGRG1 drives a protective microglial state in Alzheimer's disease through MYC activation.Neuron · 2025Article
- Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis.Biomolecules · 2025Review
- Chitosan-Based Nanoparticles Targeted Delivery System: In Treatment Approach for Dyslipidemia.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing. When fed a high fat, high cholesterol diet LXRα mutant mice rapidly develop pathologies associated with Metabolic Dysfunction-Associated Steatohepatitis (MASH) including ballooning hepatocytes, liver inflammation, and fibrosis. Strikingly LXRα mutant mice have decreased liver triglycerides but increased liver cholesterol. Therefore, elevated cholesterol in the liver may play a critical role in the development of MASH. Reengaging LXR signaling by treatment with synthetic agonist reverses MASH in LXRα mutant mice suggesting that LXRα normally functions to impede the development of liver disease.
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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 Socratic graph.