ArticleGastroenterology2011
Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 2 of them syntheses 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
165 citing papers in PubMed, 2 syntheses or guidelines pooled it, 343 citations in OpenAlex.
- High Remnant Cholesterol Increased the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) or Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review and Meta-Analysis.Journal of the ASEAN Federation of Endocrine Societies · 2026Pooled it
- The Mechanism Underlying the Influence of Indole-3-Propionic Acid: A Relevance to Metabolic Disorders.Frontiers in endocrinology · 2022Pooled it
- S100A11 regulates hepatic cholesterol metabolism and promotes steatohepatitis via noncanonical SREBP2 signaling.The Journal of clinical investigation · 2026Article
- Cholesterol Overload Drives Hepatic Steatosis by Inhibiting OGT-dependent PPARα O-GlcNAcylation and Transactivation.International journal of biological sciences · 2026Article
- Loss of LCAT function aggravates metabolic-associated steatohepatitis (MASH) in golden Syrian hamster.Clinical science (London, England : 1979) · 2025Article
- Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterology · 2025Review
- Article
- Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers ApoB-Containing Lipoproteins in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Integrative analysis of metabolomics and transcriptomics reveals alterations in egg quality and hepatic lipid metabolism in hens supplemented with curcumin.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism.Function (Oxford, England) · 2025Article
- EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis.Cell metabolism · 2025Article
- Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease.European journal of medical research · 2025Article
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Early-life antibiotic exposure aggravates hepatic steatosis through enhanced endotoxemia and lipotoxic effects driven by gutMedComm · 2025Article
- Liver magnetic resonance spectroscopy as an alternative for evaluating Niemann-Pick C disease progression.RSC advances · 2025Article
- A mutation in LXRα uncovers a role for cholesterol sensing in limiting metabolic dysfunction-associated steatohepatitis.Nature communications · 2025Article
- Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease.Journal of internal medicine · 2025Article
- 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
- Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health.Nature metabolism · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsType 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH.
methodsAlms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice.
resultsHepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis.
conclusionsIn obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH.
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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.