ArticlePloS one2013
High Fat Diet Induces Liver Steatosis and Early Dysregulation of Iron Metabolism in Rats.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 111 citations in OpenAlex.
- Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial.Hepatology (Baltimore, Md.) · 2014Trial
- Hypoglycemia and altered bile acid metabolism are linked to latent iron deficiency in young Japanese women.Journal of clinical biochemistry and nutrition · 2026Article
- Response to Letter by Ito and Mori.Kidney medicine · 2026Article
- Preclinical Application of Computer-Aided High-Frequency Ultrasound (HFUS) Imaging: A Preliminary Report on the In Vivo Characterization of Hepatic Steatosis Progression in Mouse Models.Journal of imaging · 2025Article
- Effect ofMedical sciences (Basel, Switzerland) · 2025Article
- Punicalagin relieves hepatic injury by antioxidation and enhancement of autophagy in diet-induced nonalcoholic steatohepatitis.Scientific reports · 2025Article
- Targeting cell death in NAFLD: mechanisms and targeted therapies.Cell death discovery · 2024Review
- Alisma Orientalis Extract Ameliorates Hepatic Iron Deregulation in MAFLD Mice via FXR-Mediated Gene Repression.Nutrients · 2024Article
- Distinctive protein expression in elderly livers in a Sprague-Dawley rat model of normothermic ex vivo liver machine perfusion.European journal of medical research · 2024Article
- Environmental Enrichment Prevents Gut Dysbiosis Progression and Enhances Glucose Metabolism in High-Fat Diet-Induced Obese Mice.International journal of molecular sciences · 2024Article
- Biomarkers of Metabolic Adaptation to High Dietary Fats in a Mouse Model of Obesity Resistance.Metabolites · 2024Article
- N-acetylcysteine acts as a potent anti-inflammatory agent altering the eicosanoid profile in the development of simple steatosis and its progression to hepatitis.Clinical and experimental hepatology · 2023Article
- Iron, glucose and fat metabolism and obesity: an intertwined relationship.International journal of obesity (2005) · 2023Review
- Anti-Inflammatory Effect of Ethanolic Extract fromMolecules (Basel, Switzerland) · 2023Article
- The roles of dietary lipids and lipidomics in gut-brain axis in type 2 diabetes mellitus.Journal of translational medicine · 2023Review
- Bioactive Compounds as Inhibitors of Inflammation, Oxidative Stress and Metabolic Dysfunctions via Regulation of Cellular Redox Balance and Histone Acetylation State.Foods (Basel, Switzerland) · 2023Review
- Effect of imbalance in dietary macronutrients on blood hemoglobin levels: a cross-sectional study in young underweight Japanese women.Frontiers in nutrition · 2023Article
- Article
- Betaine Alleviates High-Fat Diet-Induced Disruptionof Hepatic Lipid and Iron Homeostasis in Mice.International journal of molecular sciences · 2022Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This paper is dedicated to the memory of our wonderful colleague Professor Alfredo Colonna, who passed away the same day of its acceptance. Fatty liver accumulation, inflammatory process and insulin resistance appear to be crucial in non-alcoholic fatty liver disease (NAFLD), nevertheless emerging findings pointed an important role also for iron overload. Here, we investigate the molecular mechanisms of hepatic iron metabolism in the onset of steatosis to understand whether its impairment could be an early event of liver inflammatory injury. Rats were fed with control diet or high fat diet (HFD) for 5 or 8 weeks, after which liver morphology, serum lipid profile, transaminases levels and hepatic iron content (HIC), were evaluated. In liver of HFD fed animals an increased time-dependent activity of iron regulatory protein 1 (IRP1) was evidenced, associated with the increase in transferrin receptor-1 (TfR1) expression and ferritin down-regulation. Moreover, ferroportin (FPN-1), the main protein involved in iron export, was down-regulated accordingly with hepcidin increase. These findings were indicative of an increased iron content into hepatocytes, which leads to an increase of harmful free-iron also related to the reduction of hepatic ferritin content. The progressive inflammatory damage was evidenced by the increase of hepatic TNF-α, IL-6 and leptin, in parallel to increased iron content and oxidative stress. The major finding that emerged of this study is the impairment of iron homeostasis in the ongoing and sustaining of liver steatosis, suggesting a strong link between iron metabolism unbalance, inflammatory damage and progression of disease.
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