ArticleDiabetes & metabolism journal2016
Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice.
Article in Diabetes & metabolism journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action.Molecules (Basel, Switzerland) · 2024Pooled it
- Pooled it
- Effects of Pitavastatin on Insulin Sensitivity and Liver Fat: A Randomized Clinical Trial.The Journal of clinical endocrinology and metabolism · 2018Trial
- Simvastatin in liver diseases: therapeutic value and research advances.Clinical and experimental medicine · 2026Review
- Heart matters: How glucose- and lipid-modulating drugs remodel epicardial adipose tissue accumulation, inflammatory patterns and browning.Diabetes, obesity & metabolism · 2026Review
- Prospects of Mendelian randomization in hepatology: a comprehensive literature review with practice guidance.Clinical and molecular hepatology · 2025Review
- Lipid Accumulation and Insulin Resistance: Bridging Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Resveratrol Relieves Hepatic Steatosis and Enhances the Effects of Atorvastatin in a Mouse Model of NAFLD by Regulating the Renin-Angiotensin System, Oxidative Stress, and Inflammation.Food science & nutrition · 2025Article
- Chitinase-1 inhibition attenuates metabolic dysregulation and restores homeostasis in MASH animal models.Frontiers in immunology · 2025Article
- Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review.Archives of toxicology · 2025Review
- Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).Nutrition & metabolism · 2024Review
- Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy.World journal of gastrointestinal pathophysiology · 2024Review
- Inflammation drives pathogenesis of early intestinal failure-associated liver disease.Scientific reports · 2024Article
- Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma.Frontiers in pharmacology · 2024Review
- Atorvastatin rescues hyperhomocysteinemia-induced cognitive deficits and neuroinflammatory gene changes.Journal of neuroinflammation · 2023Article
- Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome.Respiratory research · 2023Article
- Atorvastatin Attenuates Diet-Induced Non-Alcoholic Steatohepatitis in APOE*3-Leiden Mice by Reducing Hepatic Inflammation.International journal of molecular sciences · 2023Article
- The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Effects ofMetabolites · 2022Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown.
methodsSeven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver.
resultsStatin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels.
conclusionStatins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.
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