ArticleEMBO molecular medicine2023
Inhibition of DHCR24 activates LXRα to ameliorate hepatic steatosis and inflammation.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Proteomic Analysis of Retinas from Two Different Type-1 Diabetic Models.Biomolecules · 2026Article
- Lauric-acid-rich Hermetia illucens meal modulates lipid metabolism in the liver and the fatty acid profile in piglet tissues.Scientific reports · 2026Article
- The phytosterol 24(S)-saringosterol alters lipid homeostasis and inflammatory pathways in a cell-specific manner.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Cumulative lipid exposure in young adulthood and risk of midlife MASLD.JHEP reports : innovation in hepatology · 2026Article
- Nuclear Receptor-Targeted Therapies: Reprogramming Metabolism with TRβ, ERRα, and LXR Modulators.Biomolecules · 2026Review
- The sterols-LXR axis alleviates IL-17-mediated acute inflammatory response inMarine life science & technology · 2026Article
- A proteomics and redox proteomics approach to understanding ARDS heterogeneity.Scientific reports · 2026Article
- Desmosterol as a Novel Biomarker Linking Cholesterol Metabolism, Liver Inflammation, and Cardiovascular Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of atherosclerosis and thrombosis · 2026Article
- DNAJB4 Protects Against Atherosclerosis by Stabilizing the HSP70-LXRα Axis in Hepatic Lipid Metabolism.International journal of biological sciences · 2026Article
- The Selective DHCR24 Blocker SH42 Inhibits ACE2 Binding and Cellular Entry of SARS-CoV-2 Spike Proteins More Efficiently Than Atorvastatin.Research (Washington, D.C.) · 2026Article
- DHCR24 Drives Ovarian Cancer Chemoresistance Through Lipid Raft-mediated P-gp Stabilization and STAT3 Activation.International journal of biological sciences · 2026Article
- DHCR24 Deficiency Drives Age-Related Meibomian Gland Dysfunction by Regulating Lipid Metabolic Imbalance and Cytosolic mtDNA-Induced cGAS-STING Activation.International journal of biological sciences · 2026Article
- Serum Desmosterol Level Reflects Hepatic Inflammation Grade in Patients with Biopsy-Confirmed Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of atherosclerosis and thrombosis · 2026Article
- Research Status and Latest Progress in the Regulatory Mechanisms of ABCA1.International journal of molecular sciences · 2025Review
- Innate immune cell LXR-β deficiency exacerbates hepatic injury and fibrosis in murine models of primary sclerosing cholangitis.Liver research (Beijing, China) · 2025Article
- Pan-cancer analysis reveals the potential role of DHCR24 in bladder cancer via interactions with HRAS to facilitate cholesterol synthesis.Oncology letters · 2025Article
- Liver X Receptor Activation Alleviates Hepatic Ischemia-Reperfusion Injury in Diabetes by Inhibiting NF-κB-NLRP3 Activation.Immunity, inflammation and disease · 2025Article
- Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH.Cell reports. Medicine · 2025Article
- Insights into the renal pathophysiology in Hermansky-Pudlak syndrome-1 from urinary extracellular vesicle proteomics and a new mouse model.FEBS letters · 2025Article
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Authors and funding
17 authors.
Funding
Abstract
Liver X receptor (LXR) agonism has theoretical potential for treating NAFLD/NASH, but synthetic agonists induce hyperlipidemia in preclinical models. Desmosterol, which is converted by Δ24-dehydrocholesterol reductase (DHCR24) into cholesterol, is a potent endogenous LXR agonist with anti-inflammatory properties. We aimed to investigate the effects of DHCR24 inhibition on NAFLD/NASH development. Here, by using APOE*3-Leiden. CETP mice, a well-established translational model that develops diet-induced human-like NAFLD/NASH characteristics, we report that SH42, a published DHCR24 inhibitor, markedly increases desmosterol levels in liver and plasma, reduces hepatic lipid content and the steatosis score, and decreases plasma fatty acid and cholesteryl ester concentrations. Flow cytometry showed that SH42 decreases liver inflammation by preventing Kupffer cell activation and monocyte infiltration. LXRα deficiency completely abolishes these beneficial effects of SH42. Together, the inhibition of DHCR24 by SH42 prevents diet-induced hepatic steatosis and inflammation in a strictly LXRα-dependent manner without causing hyperlipidemia. Finally, we also showed that SH42 treatment decreased liver collagen content and plasma alanine transaminase levels in an established NAFLD model. In conclusion, we anticipate that pharmacological DHCR24 inhibition may represent a novel therapeutic strategy for treatment of NAFLD/NASH.
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