ArticleFree radical biology & medicine2013
Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- TM4SF5-mediated KEAP1 Regulation in Hepatocytes Irrelevant to NRF2 Expression and Activity Promotes Oxidative Stress and Inflammation to Develop Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of biological sciences · 2026Article
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- The effect and mechanism of Germacrone in ameliorating alcoholic fatty liver by inhibiting Nrf2/Rbp4.Chinese medicine · 2025Article
- Mechanism of valproic acid-induced hepatic steatosis via enhancing NRF2-FATP2-mediated fatty acid uptake.Theranostics · 2025Article
- The protective effects of fisetin in metabolic disorders: a focus on oxidative stress and associated events.Journal of diabetes and metabolic disorders · 2024Review
- Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.Antioxidants (Basel, Switzerland) · 2024Article
- Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity.The Journal of clinical investigation · 2023Article
- A Review of the Potential of Nuclear Factor [Erythroid-Derived 2]-like 2 Activation in Autoimmune Diseases.Brain sciences · 2023Review
- The Nrf2 in Obesity: A Friend or Foe?Antioxidants (Basel, Switzerland) · 2022Review
- Sulforaphane suppresses the activity of sterol regulatory element-binding proteins (SREBPs) by promoting SREBP precursor degradation.Scientific reports · 2022Article
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- A Role of Stress Sensor Nrf2 in Stimulating Thermogenesis and Energy Expenditure.Biomedicines · 2021Review
- Perfluorooctanesulfonic Acid (PFOS) Thwarts the Beneficial Effects of Calorie Restriction and Metformin.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Liver Fibrosis-From Mechanisms of Injury to Modulation of Disease.Frontiers in medicine · 2021Review
- Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects.Antioxidants (Basel, Switzerland) · 2020Review
- Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.International journal of molecular sciences · 2020Review
- Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.Redox biology · 2020Article
- Article
- Modulating NRF2 in Disease: Timing Is Everything.Annual review of pharmacology and toxicology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome.
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