ArticleToxicology and applied pharmacology2012
Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet.
Article in Toxicology and applied pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
- NRF2 activation attenuates obesity-induced adipose inflammation by suppressing STING signaling, with depot-specific regulation.Journal of translational medicine · 2026Article
- NRF2 Deficiency Disrupts Mitochondrial Homeostasis via NDUFS7 in Trabecular Meshwork.Research (Washington, D.C.) · 2026Article
- Nrf2 Overexpression in Spontaneously Hypertensive Rats Enhances Adipose Tissue Metabolism through Redox-Mediated Suppression of Mitochondrial Oxidative Phosphorylation.Physiological research · 2025Article
- FGF9 alleviates diabetic cardiomyopathy by activating Nrf2 via SQSTM1/p62-Keap1 in mice.Communications biology · 2025Article
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Nuclear factor erythroid 2-related factor 2 ameliorates disordered glucose and lipid metabolism in liver: Involvement of gasdermin D in regulating pyroptosis.Clinical and translational medicine · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus.Probiotics and antimicrobial proteins · 2024Review
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- Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation.Frontiers in pharmacology · 2024Article
- Higher pNRF2, SOCS3, IRF3, and RIG1 Tissue Protein Expression in NASH Patients versus NAFL Patients: pNRF2 Expression Is Concomitantly Associated with Elevated Fasting Glucose Levels.Journal of personalized medicine · 2023Article
- Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease.World journal of gastroenterology · 2022Review
- Monkfish (Molecules (Basel, Switzerland) · 2022Article
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- The Nrf2 in Obesity: A Friend or Foe?Antioxidants (Basel, Switzerland) · 2022Review
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- Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling.
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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.