ArticleRedox biology2022
Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation.
Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 106 citations in OpenAlex.
- Analysis of the Mediating Role of Cytokines in the Relationship Between Nonalcoholic Fatty Liver Disease and Cognitive Impairment After Ischemic Stroke.Brain and behavior · 2026Article
- GDF15: A Hijacked Metabo-Hormone Orchestrating Cachexia and Immunosuppression in Cancer.Biomolecules · 2026Review
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- KLF5-driven TAZ-FASN signaling reprograms fatty acid metabolism to support Treg differentiation in lung cancer.Journal of translational medicine · 2026Article
- Mometasone Furoate Alleviates PM2.5-Induced Pyroptosis of Nasal Mucosa Cells via Blocking JAK2/STAT3/AIM2 Inflammasome.Immunity, inflammation and disease · 2026Article
- The challenge of cell death switching in inflammasome-targeted therapies for bacterial and viral infections.Communications biology · 2026Review
- Bisphosphoglycerate mutase is involved in glucose metabolism and progression of nonalcoholic fatty liver disease based on liver organoids.Human cell · 2026Article
- Multi-target regulation by artemether in MAFLD through EGFR/HSP90 pathways.Journal of advanced research · 2026Article
- Growth differentiation factor 15 mitigates lipotoxic steatosis by preserving mitochondrial morphodynamics and augmenting fatty acid oxidation in hepatocytes and liver organoids.Diabetes, obesity & metabolism · 2026Article
- Cardiovascular risk assessment characterized by proteomics in cancer survivors.Communications medicine · 2026Article
- Fatty acid-induced lipid accumulation promotes radiosensitization in Huh7 hepatocellular carcinoma cells.Oncology letters · 2026Article
- Melatonin Alleviates Cerebral Ischemia/Reperfusion Injury by Mitigating AIM2-Mediated PANoptosis in Ischemic Penumbra.Molecular neurobiology · 2026Article
- NRF1 is upregulated by docosahexaenoic acid to ameliorate MASH through the inhibition of ER stress.Cell death & disease · 2026Article
- The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment Modulation.International journal of biological sciences · 2026Review
- GPER1 as a therapeutic target in MASLD: evidence for steatosis attenuation by agonist G1 in preclinical models.Frontiers in pharmacology · 2026Article
- Growth Differentiation Factor 15 (GDF-15) as a modulator of hepatic steatosis and fibrosis: insights from a 6-year retrospective cohort study.Frontiers in medicine · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Smilax glabra flavonoids ameliorate non-alcoholic steatohepatitis by regulating PKM2-dependent glycolysis and suppressing AIM2 inflammasome activation.Frontiers in immunology · 2026Article
- SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling.Journal of neuroinflammation · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction and oxidative stress-mediated inflammasome activation play critical roles in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), or growth differentiation factor-15 (GDF15), is associated with many biological processes and diseases, including NAFLD. However, the role of NAG-1/GDF15 in regulating oxidative stress and whether this process is associated with absent in melanoma 2 (AIM2) inflammasome activation in NAFLD are unknown. In this study, we revealed that NAG-1/GDF15 is significantly downregulated in liver tissues of patients with steatosis compared to normal livers using the Gene Expression Omnibus (GEO) database, and in free fatty acids (FFA, oleic acid/palmitic acid, 2:1)-induced HepG2 and Huh-7 cellular steatosis models. Overexpression of NAG-1/GDF15 in transgenic (Tg) mice significantly alleviated HFD-induced obesity and hepatic steatosis, improved lipid homeostasis, enhanced fatty acid β-oxidation and lipolysis, inhibited fatty acid synthesis and uptake, and inhibited AIM2 inflammasome activation and the secretion of IL-18 and IL-1β, as compared to their wild-type (WT) littermates without reducing food intake. Furthermore, NAG-1/GDF15 overexpression attenuated FFA-induced triglyceride (TG) accumulation, lipid metabolism deregulation, and AIM2 inflammasome activation in hepatic steatotic cells, while knockdown of NAG-1/GDF15 demonstrated opposite effects. Moreover, NAG-1/GDF15 overexpression inhibited HFD- and FFA-induced oxidative stress and mitochondrial damage which in turn reduced double-strand DNA (dsDNA) release into the cytosol, while NAG-1/GDF15 siRNA showed opposite effects. The reduced ROS production and dsDNA release may be responsible for attenuated AIM2 activation by NAG-1/GDF15 upon fatty acid overload. In conclusion, our results provide evidence that other than regulating lipid homeostasis, NAG-1/GDF15 protects against hepatic steatosis through a novel mechanism via suppressing oxidative stress, mitochondrial damage, dsDNA release, and AIM2 inflammasome activation.
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