ArticleRedox biology2020
Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Who cites it
63 citing papers in PubMed, 111 citations in OpenAlex.
- Hepatocyte-SpecificAntioxidants (Basel, Switzerland) · 2026Article
- Nrf2 deficiency in myeloid cells accelerates atherosclerosis by promoting the inflammatory response and impairing efferocytosis.Journal of advanced research · 2026Article
- Probucol inhibits palmitic acid-mediated renal calcium oxalate stone formation by targeting KLF5-PPARγ axis-mediated lipotoxicity.Journal of pharmaceutical analysis · 2026Article
- Molecular Mechanisms and Targeted Therapies of PTPN2 in Metabolic Diseases: A Review.Biomolecules · 2026Review
- Hugan Tablets Alleviate Alcoholic Liver Injury by Modulating Hepatic Glutathione Metabolism and PPARγ/NRF2/GPX4-Related Antioxidant Defense.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The dual roles of natural cannabidiol in combating oxidative stress and inflammation: A potential intestinal guardian.Redox biology · 2026Review
- Mechanism of Liver Injury Induced by CrAnimals : an open access journal from MDPI · 2026Article
- Article
- Decoding the CHI3L1/IL-13Rα2 signaling nexus in MASH-fibrosis pathogenesis.Science advances · 2025Article
- NRF2-REGγ-ACADM/KLF15 Signaling Pathway Regulates the Browning of White Adipose Tissue to Modulate Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PPARγ-Axl axis ameliorates intervertebral disc degeneration by activating PI3K/AKT-mediated autophagy to suppress ferroptosis.Cellular & molecular biology letters · 2025Article
- Review
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- The impact of a high-fat diet on liver health in pregnant mice and their offspring: The role of the gut-liver axis.iMetaOmics · 2025Article
- ECM1 expression in chronic liver disease: Regulation by EGF/STAT1 and IFNγ/NRF2 signalling.JHEP reports : innovation in hepatology · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- ELANE enhances KEAP1 protein stability and reduces NRF2-mediated ferroptosis inhibition in metabolic dysfunction-associated fatty liver disease.Cell death & disease · 2025Article
- Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer.Molecular biotechnology · 2025Article
- 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
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an emerging global disease with increasing prevalence. However, the mechanism of NAFLD development is not fully understood. To elucidate the cell-specific role of nuclear factor erythroid-derived 2-like 2 (NRF2) in the pathogenesis of NAFLD, we utilized hepatocyte- and macrophage-specific Nrf2-knockout [Nrf2(L)-KO and Nrf2(Mϕ)-KO] mice to examine the progress of NAFLD induced by high-fat diet (HFD). Compared to Nrf2-LoxP littermates, Nrf2(L)-KO mice showed less liver enlargement, milder inflammation and less hepatic steatosis after HFD feeding. In contrast, Nrf2(Mϕ)-KO mice displayed no significant difference in HFD-induced hepatic steatosis from Nrf2-LoxP control mice. Mechanistic investigations revealed that Nrf2 deficiency in hepatocytes dampens the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its downstream lipogenic genes in the liver and/or primary hepatocytes induced by HFD and palmitate exposure, respectively. While PPARγ agonists augmented PPARγ expression and its transcriptional activity in primary hepatocytes in a NRF2-dependent manner, forced overexpression of PPARγ1 or γ2 distinctively reversed the decreased expression of their downstream genes fatty acid binding protein 4, lipoprotein lipase and/or fatty acid synthase caused by Nrf2 deficiency. We conclude that NRF2-dependent expression of PPARγ in hepatocytes is a critical initiating process in the development of NAFLD, suggesting that inhibition of NRF2 specifically in hepatocytes may be a valuable approach to prevent the disease.
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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.