ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- TCM-Guided Targeted Therapies Against NLRP3 Inflammasome in NAFLD.Immunity, inflammation and disease · 2026Review
- Cholesterol metabolism dysregulated by key HBV mutations revealed through multi-omics profiling.iScience · 2026Article
- Lipid metabolism-MAFLD crosstalk: mechanisms and therapy.Frontiers in endocrinology · 2026Review
- The dynamic trajectory of circulating exosome components in high-fat diet-induced metabolic-associated steatotic liver disease and its modulation by curcuminoids.Frontiers in endocrinology · 2026Article
- Loss of LCAT function aggravates metabolic-associated steatohepatitis (MASH) in golden Syrian hamster.Clinical science (London, England : 1979) · 2025Article
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Integrated Lipidomics and Network Pharmacology Reveal the AMPK-Mediated Therapeutic Mechanism of 3,3'-Diindolylmethane in Hepatic Lipid Metabolism.Antioxidants (Basel, Switzerland) · 2025Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.Biomolecules · 2025Review
- Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Therapeutic Targeting of PPARγ in Nonalcoholic Fatty Liver Disease: Efficacy, Safety, and Drug Development.Drug design, development and therapy · 2025Review
- Catalpol-a compound fromFrontiers in microbiology · 2025Article
- Targeting the gut microbiota and lipid metabolism: potential mechanisms of natural products for the treatment of non-alcoholic fatty liver disease.Frontiers in pharmacology · 2025Review
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7 authors.
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Abstract
Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls. The FC level demonstrated a positive correlation with the ALT level in both patients and mice. Mechanistic studies revealed that FC elevated reactive oxygen species level, impaired the function of lysosomes, and disrupted lipophagy process, consequently inducing cell apoptosis. We then found that DhT protected mice on an HCD diet, independent of gut microbiota. DhT functioned as a potent ligand for peroxisome proliferator-activated receptor α (PPARα), stimulating its transcriptional function and enhancing catalase expression to lower reactive oxygen species (ROS) level. Notably, the protective effect of DhT was nullified in mice with hepatic PPARα knockdown. Thus, these findings are the first to report the detrimental role of FC in NAFLD, which could lead to the development of new treatment strategies for NAFLD by leveraging the therapeutic potential of DhT and PPARα pathway.
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