ArticleJCI insight2018
Nrf2 prevents Notch-induced insulin resistance and tumorigenesis in mice.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Nrf2 Hyperactivation as a Driver of Radiotherapy Resistance and Suppressed Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine.The EPMA journal · 2025Article
- Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.Nitric oxide : biology and chemistry · 2024Article
- A Notch toward Progenitor D(G)FRentiation: Defining a NOTCH-PDGFR axis in brown adipogenesis.Developmental cell · 2024Article
- Dual Deletion ofInternational journal of molecular sciences · 2024Article
- SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling.Nature communications · 2023Article
- ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production.Nature communications · 2023Article
- Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model.International journal of molecular sciences · 2023Article
- Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies.International journal of molecular sciences · 2023Article
- The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.Molecules and cells · 2023Review
- Maternal Calorie Restriction Induces a Transcriptional Cytoprotective Response in Embryonic Liver Partially Dependent on Nrf2.Antioxidants (Basel, Switzerland) · 2022Article
- The Nrf2 in Obesity: A Friend or Foe?Antioxidants (Basel, Switzerland) · 2022Review
- The Therapeutic Potential of Kaemferol and Other Naturally Occurring Polyphenols Might Be Modulated by Nrf2-ARE Signaling Pathway: Current Status and Future Direction.Molecules (Basel, Switzerland) · 2022Review
- Upregulation of Anti-Oxidative Stress Response Improves Metabolic Changes in L-Selectin-Deficient Mice but Does Not Prevent NAFLD Progression or Fecal Microbiota Shifts.International journal of molecular sciences · 2021Article
- Fructose and the Liver.International journal of molecular sciences · 2021Review
- The Role of Notch Signaling Pathway in Non-Alcoholic Fatty Liver Disease.Frontiers in molecular biosciences · 2021Review
- Mice Hypomorphic forThyroid : official journal of the American Thyroid Association · 2021Article
- The Keap1/Nrf2 Signaling Pathway in the Thyroid-2020 Update.Antioxidants (Basel, Switzerland) · 2020Review
- The Role of the Nrf2 Signaling in Obesity and Insulin Resistance.International journal of molecular sciences · 2020Review
- Sesamol Increases Ucp1 Expression in White Adipose Tissues and Stimulates Energy Expenditure in High-Fat Diet-Fed Obese Mice.Nutrients · 2020Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Insulin resistance is associated with increased incidence and enhanced progression of cancers. However, little is known about strategies that can effectively ameliorate insulin resistance and consequently halt cancer progression. Herein, we propose that the transcription factor Nrf2 (also known as Nfe2l2) may be such a target, given its central role in disease prevention. To this end, we developed a mouse that overexpresses the Notch intracellular domain in adipocytes (AdNICD), leading to lipodystrophy-induced severe insulin resistance and subsequent development of sarcomas, as a model reflecting that Notch signaling is deregulated in cancers and shows positive associations with insulin resistance and fatty liver disease in humans. Nrf2 pathway activation was achieved by knocking down Keap1, a repressor of Nrf2, in the AdNICD background. Constitutively enhanced Nrf2 signaling in this setting led to prevention of hepatic steatosis, dyslipidemia, and insulin resistance by repressing hepatic lipogenic pathways and restoration of the hepatic fatty acid profile to control levels. This protective effect of Nrf2 against diabetes extended to significant reduction and delay in sarcoma incidence and latency. Our study highlights that the Nrf2 pathway, which has been induced by small molecules in clinical trials, is a potential therapeutic target against insulin resistance and subsequent risk of cancer.
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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.