ArticleLaboratory investigation; a journal of technical methods and pathology2019
Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Therapeutic potential of mesenchymal stem cell-derived extracellular vesicle in nonalcoholic fatty liver disease: a systematic review and meta-analysis of preclinical evidence.Lipids in health and disease · 2025Pooled it
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.Inflammation · 2026Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- The therapeutic potential of botanicals: how medicinal plants targeting autophagy can reverse metabolic-associated fatty liver disease.Frontiers in pharmacology · 2026Review
- Quercetin prevents age-related hearing loss in C57BL/6J mice by activating mitophagy and inhibiting the NLRP3 inflammasome.PloS one · 2026Article
- Cells with Defective Mitophagy Do Not Accumulate Atherogenic LDL-Derived Cholesterol.Current medicinal chemistry · 2026Article
- Ethnic-specific ZJU index thresholds for hepatic steatosis and fibrosis in Chinese MASLD.Frontiers in medicine · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Modulation of Inflammation-Driven Hepatocarcinogenesis: The Hepatic Immune Microenvironment, Gut-Liver Axis, and Neuroregulation.Journal of hepatocellular carcinoma · 2026Review
- The NLRP3 inflammasome in metabolic dysfunction-associated steatotic liver disease: role and advances in therapeutic targeting.Frontiers in immunology · 2026Review
- Postprandial Inflammation in Obesity: Dietary Determinants, Adipose Tissue Dysfunction and the Gut Microbiome.Biomolecules · 2025Review
- Review
- Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy.bioRxiv : the preprint server for biology · 2025Article
- Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2.Scientific reports · 2025Article
- Disrupted host-microbiota crosstalk promotes nonalcoholic fatty liver disease progression by impaired mitophagy.Microbiology spectrum · 2025Article
- Loss of ovarian function prevents exercise-induced activation of hepatic mitophagic flux.American journal of physiology. Endocrinology and metabolism · 2025Article
- Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial.Life (Basel, Switzerland) · 2025Article
- Autophagy: a double-edged sword in ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- Mitochondrial alterations and signatures in hepatocellular carcinoma.Cancer metastasis reviews · 2025Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
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Abstract
Activation of inflammation is an important mechanism in the development of nonalcoholic steatohepatitis (NASH). This study aims to delineate how mitophagy affects NLRP3 inflammasome activation in hepatic lipotoxicity. Mice were fed a high fat/calorie diet (HFCD) for 24 weeks. Primary rat hepatocytes were treated with palmitic acid (PA) for various periods of time. Mitophagy was measured by protein levels of LC3II and P62. NLRP3, caspase-1, interleukin (IL)-18, and IL-1β at mRNA and protein levels were used as indicators of inflammasome activation. Along with steatotic progression in HFCD-fed mice, ratio of LC3II/β-actin was decreased concurrently with increased levels of liver P62, NLRP3, caspase-1, IL-1β, IL-18, and serum IL-1β levels in late-stage NASH. PA treatment resulted in mitochondrial oxidative stress and initiated mitophagy in primary hepatocytes. The addition of cyclosporine A did not change LC3II/Τοmm20 ratios; but P62 levels were increased after an extended duration of PA exposure, indicating a defect in autophagic activity. Along with impaired mitophagy, mRNA and protein levels of NLRP3, caspase-1, IL-18 and IL-1β were upregulated by PA treatment. Pretreatment with MCC950, N-acetyl cysteine or acetyl-L-carnitine reversed inflammasome activation and a pyroptotic cascade. Additionally, mitophagic flux was partially recovered as indicated by increases in LC3II/Tomm20 ratio, parkin, and PINK1 expression, and decreased P62 expression. The findings suggest that impaired mitophagy triggers hepatic NLRP3 inflammasome activation in a murine NASH model and primary hepatocytes. The new insights into inflammasome activation through mitophagy advance our understanding of how fatty acids elicit lipotoxicity through oxidant stress and autophagy in mitochondria.
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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.