ArticleArchives of biochemistry and biophysics2016
Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet.
Article in Archives of biochemistry and biophysics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 101 citations in OpenAlex.
- Obesity-associated unfolded protein response, oxidative stress, and NRF2 signaling.International journal of obesity (2005) · 2026Review
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- FGF9 alleviates diabetic cardiomyopathy by activating Nrf2 via SQSTM1/p62-Keap1 in mice.Communications biology · 2025Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- NRF2 Activation Suppressed Methylglyoxal-Lysine Dimer-Induced Oxidative Stress and Inflammatory Paracrine Interaction between Macrophages and Adipocytes.Preventive nutrition and food science · 2025Article
- Effects of Nutritional Disturbances on the Structure and Function of Mitochondria, Oxidative Stress Level, and Fat Deposition in Chicken Liver Cells.Animals : an open access journal from MDPI · 2025Article
- Adipose cullin 3 mediates the antiobesity effect of pan neddylation inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Portulaca oleracea-derived indoline amide ameliorates obesity and NAFLD in rats through Nrf2-dependent antioxidant and anti-inflammatory mechanisms.Scientific reports · 2025Article
- Aloesin activates Nrf2 signaling to attenuate obesity-associated oxidative stress and hepatic steatosis in high-fat diet-fed rats.Scientific reports · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Article
- Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.Nitric oxide : biology and chemistry · 2024Article
- Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.Nature communications · 2024Article
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
- The protective role of resveratrol against high glucose-induced oxidative stress and apoptosis in HepG2 cells.Food science & nutrition · 2024Article
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation.Frontiers in pharmacology · 2024Article
- Nrf2 modulates the benefits of evening exercise in type 2 diabetes.Sports medicine and health science · 2023Review
- Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model.International journal of molecular sciences · 2023Article
- Nrf2-Mediated Antioxidant Defense and Thyroid Hormone Signaling: A Focus on Cardioprotective Effects.Antioxidants (Basel, Switzerland) · 2023Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The Keap1/Nrf2 pathway, known to regulate the expression of a series of cytoprotective and antioxidant genes, has been studied in the context of obesity and type 2 diabetes; diseases that are characterized by chronic oxidative stress. There is increasing evidence, however, that the transcription factor Nrf2 can crosstalk with pathways not directly related to cytoprotection. Our present work focuses on the effect of Nrf2 on hepatic gluconeogenesis and lipogenesis, two metabolic processes which are dysregulated in the obese/diabetic state. To this end, a genetic mouse model of Nrf2 pathway activation was used (Keap1-hypo; both Keap1 alleles are hypomorphic) and was exposed to a 3-month high-fat diet along with the relevant control wild-type mice. The Keap1-hypo mice were partially protected from obesity, had lower fasting glucose and insulin levels and developed less liver steatosis compared to the wild-type. Key gluconeogenic and lipogenic enzymes were repressed in the Keap1-hypo livers with concomitant activated Ampk signaling. Primary Keap1-hypo hepatocyte cultures also show increased Ampk signaling and repressed glucose production. In conclusion, increased Keap1/Nrf2 signaling in the liver is accompanied by repressed gluconeogenesis and lipogenesis that can, at least partially, explain the ameliorated diabetic phenotype in the Keap1-hypo mice.
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Registered trials
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