ArticleGastroenterology2012
A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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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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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
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- From mechanisms to anti-fibrotic drugs in hepatic stellate cell research: a global bibliometric analysis with patent and clinical perspectives (2000-2025).Frontiers in pharmacology · 2025Pooled it
- Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.Journal of lipid research · 2015Trial
- The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial.Diabetologia · 2014Trial
- Nine-Week Co-Supplementation with Sugarcane Wax Alcohol (Policosanol), Phosphatidylserine, andInternational journal of molecular sciences · 2026Article
- Protective Effects of Policosanol and Atorvastatin Co-Supplementation Against High-Cholesterol and High-Galactose Diet-Induced Metabolic and Organ Dysfunction in Zebrafish.International journal of molecular sciences · 2026Article
- Therapeutic targeting of AREL1 in hepatic stellate cells attenuates MASH-related liver fibrosis.Nature communications · 2026Article
- DN203316, a novel PPARδ agonist, suppresses ferroptotic signaling and fibrogenesis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2026Article
- Paocai-derived Lactiplantibacillus plantarum NMG11 can maintain lipid metabolic homeostasis, alleviate inflammation, and remodel the gut microbiota in high-cholesterol diet-fed mice.Probiotics and antimicrobial proteins · 2026Article
- Annexin A2 Is Associated with Dietary Cholesterol-Induced Metabolic Dysregulation and the Progression of Hepatic Fibrosis.Metabolites · 2026Article
- Ligature-induced periodontitis exacerbates high-carbohydrate/high-fat diet-induced fatty liver in mice under non-diabetic conditions.BMC oral health · 2026Article
- Combination of Policosanol (RaydelPharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Cuban Sugarcane Wax Alcohol Supplementation Prevents Brain and Eye Damages of Zebrafish Exposed to High-Cholesterol and High-Galactose Diet for 30 Weeks: Protection of Myelin, Cornea, and Retina.Antioxidants (Basel, Switzerland) · 2025Article
- Ferroptosis in liver fibrosis and its potential intervention strategy.Cell biology and toxicology · 2025Review
- Loss of LCAT function aggravates metabolic-associated steatohepatitis (MASH) in golden Syrian hamster.Clinical science (London, England : 1979) · 2025Article
- Adverse Effect of Sugarcane Extract Powder (SEP) in Hyper-Lipidemic Zebrafish During a 14-Week Diet: A Comparative Analysis of Biochemical and Toxicological Efficacy Between Four SEPs and Genuine Policosanol (RaydelInternational journal of molecular sciences · 2025Article
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Liver immunology: Biological role and clinical significance.World journal of hepatology · 2025Review
- Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): data from the NHANES III (1988-1994).Nutrition & metabolism · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsSome studies have indicated that dietary cholesterol has a role in the progression of liver fibrosis. We investigated the mechanisms by which dietary cholesterol might contribute to hepatic fibrogenesis.
methodsC57BL/6 mice were fed a high-cholesterol diet or a control diet for 4 weeks; liver fibrosis then was induced by bile-duct ligation or carbon tetrachloride administration. Hepatic stellate cells (HSCs) were isolated from mice fed high-cholesterol diets or from Niemann-Pick type C1-deficient mice, which accumulate intracellular free cholesterol.
resultsAfter bile-duct ligation or carbon tetrachloride administration, mice fed high-cholesterol diets had significant increases in liver fibrosis and activation of HSCs compared with mice fed control diets. There were no significant differences in the degree of hepatocellular injury or liver inflammation, including hepatocyte apoptosis or Kupffer cell activation, between mice fed high-cholesterol or control diets. Levels of free cholesterol were much higher in HSCs from mice fed high-cholesterol diets than those fed control diets. In cultured HSCs, accumulation of free cholesterol in HSCs increased levels of Toll-like receptor 4 (TLR4), leading to down-regulation of bone morphogenetic protein and activin membrane-bound inhibitor (a pseudoreceptor for transforming growth factor [TGF]β); the HSCs became sensitized to TGFβ-induced activation. Liver fibrosis was not aggravated by the high-cholesterol diet in C3H/HeJ mice, which express a mutant form of TLR4; HSCs that express mutant TLR4 were not activated by accumulation of free cholesterol.
conclusionsDietary cholesterol aggravates liver fibrosis because free cholesterol accumulates in HSCs, leading to increased TLR4 signaling, down-regulation of bone morphogenetic protein and activin membrane-bound inhibitor, and sensitization of HSC to TGFβ. This pathway might be targeted by antifibrotic therapies.
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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 OpenQuestion graph.