ArticleBiochemical pharmacology2010
Eicosapentaenoic acid improves hepatic steatosis independent of PPARα activation through inhibition of SREBP-1 maturation in mice.
Article in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
The trial behind it
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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Effects of omega-3 supplementation on lipid metabolism, inflammation, and disease activity in rheumatoid arthritis: a meta-analysis of randomized controlled trials.Clinical rheumatology · 2024Pooled it
- Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis.The British journal of nutrition · 2012Pooled it
- Identification of Phenotypic Lipidomic Signatures in Response to Long Chain n-3 Polyunsaturated Fatty Acid Supplementation in Humans.Journal of the American Heart Association · 2021Trial
- SREBF1 gene variations modulate insulin sensitivity in response to a fish oil supplementation.Lipids in health and disease · 2014Trial
- Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation.Journal of lipid research · 2013Trial
- Hepatocyte PPARα Is Essential for Triglyceride-Lowering Effect of Pemafibrate.International journal of molecular sciences · 2026Article
- Article
- Eryptosis in Liver Diseases: Contribution to Anemia and Hypercoagulation.Medical sciences (Basel, Switzerland) · 2025Review
- DietaryNutrients · 2025Article
- Anti-Inflammatory Activity of the Constituents from the Leaves ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Adipose-targeted SWELL1 deletion exacerbates obesity- and age-related nonalcoholic fatty liver disease.JCI insight · 2023Article
- Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.Current atherosclerosis reports · 2022Review
- Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes.Nutrients · 2022Review
- Is there a role of lipid-lowering therapies in the management of fatty liver disease?World journal of hepatology · 2022Review
- Article
- Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired β-cell function.iScience · 2021Article
- Omega-3 polyunsaturated fatty acids: anti-inflammatory and anti-hypertriglyceridemia mechanisms in cardiovascular disease.Molecular and cellular biochemistry · 2021Review
- The Dietary Replacement of Soybean Oil by Canola Oil Does Not Prevent Liver Fatty Acid Accumulation and Liver Inflammation in Mice.Nutrients · 2020Article
- Mediterranean diet for patients with non-alcoholic fatty liver disease, a systematic review and meta-analysis of observational and clinical investigations.Journal of diabetes and metabolic disorders · 2020Review
- Dietary and Pharmacological Fatty Acids and Cardiovascular Health.The Journal of clinical endocrinology and metabolism · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis. However, it remains unclear whether such action of EPA is actually caused by peroxisome proliferator-activated receptor α (PPARα) activation. To explore the contribution of PPARα to the effects of EPA itself, male wild-type and Ppara-null mice were fed a saturated fat diet for 16 weeks, and highly (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the changes caused by EPA treatment were compared to those elicited by fenofibrate (FF), a typical PPARα activator. A saturated fat diet caused macrovesicular steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type mice without PPARα activation, which was evidently different from numerous previous observations. Instead, EPA inhibited maturation of sterol-responsive element-binding protein (SREBP)-1 in the presence of PPARα through down-regulation of SREBP cleavage-activating protein and site-1 protease. Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of intrahepatic triglycerides in a PPARα-independent manner. These effects were distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides, EPA caused PPARα-dependent induction of superoxide dismutases, probably contributing to a decrease in the lipid peroxides. These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPARα activation and ensuing augmentation of hepatic oxidative stress.
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Registered trials
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