ArticleJournal of hepatology2013
Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis.
Article in Journal of hepatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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Who cites it
72 citing papers in PubMed, 128 citations in OpenAlex.
- Distinct Plasma Proteomic Signatures Distinguish MASLD From Non-Steatotic Individuals but Not From MetALD.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Adipokines as Regulators of Nitric Oxide Synthase Isoforms Across Organs: Emerging Implications for Gastrointestinal Motility.International journal of molecular sciences · 2026Review
- Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2025Review
- Arctigenin Prevents Metabolic Dysfunction-associated Steatohepatitis by Inhibiting NLRP3/GSDMD-N Axis in Macrophages.Journal of clinical and translational hepatology · 2025Article
- The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Nonlinear relationship between serum high sensitivity C reactive protein to high density lipoprotein cholesterol ratio with non-alcoholic fatty liver disease.Scientific reports · 2025Article
- Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.Clinical and molecular hepatology · 2024Review
- Interleukin-1β Signaling Contributes to Cell Cycle Arrest and Apoptotic Cell Death by Leptin via Modulation of AKT and p38MAPK in Hepatocytes.Biomolecules & therapeutics · 2024Article
- Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.International journal of molecular sciences · 2024Review
- A bibliometric analysis of macrophages associated with non-alcoholic fatty liver disease research from 2005 to 2023.Heliyon · 2024Article
- Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit.International journal of molecular sciences · 2023Article
- Hepatic inflammatory responses in liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- Associations between Oxidant/Antioxidant Status and Circulating Adipokines in Non-Obese Children with Prader-Willi Syndrome.Antioxidants (Basel, Switzerland) · 2023Article
- Detangling the interrelations between MAFLD, insulin resistance, and key hormones.Hormones (Athens, Greece) · 2022Review
- Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging.International journal of molecular sciences · 2022Review
- Immunohistochemical identification and assessment of the location of leptin, visfatin and chemerin in the liver of men with different body mass index.BMC gastroenterology · 2022Article
- Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsProgression from steatosis to steatohepatitic lesions is hypothesized to require a second hit. These lesions have been associated with increased oxidative stress, often ascribed to high levels of leptin and other proinflammatory mediators. Here we have examined the role of leptin in inducing oxidative stress and Kupffer cell activation in CCl4-mediated steatohepatitic lesions of obese mice.
methodsMale C57BL/6 mice fed with a high-fat diet (60%kcal) at 16 weeks were administered CCl₄ to induce steatohepatitic lesions. Approaches included use of immuno-spin trapping for measuring free radical stress, gene-deficient mice for leptin, p47 phox, iNOS and adoptive transfer of leptin primed macrophages in vivo.
resultsDiet-induced obese (DIO) mice, treated with CCl4 increased serum leptin levels. Oxidative stress was significantly elevated in the DIO mouse liver, but not in ob/ob mice, or in DIO mice treated with leptin antibody. In ob/ob mice, leptin supplementation restored markers of free radical generation. Markers of free radical formation were significantly decreased by the peroxynitrite decomposition catalyst FeTPPS, the iNOS inhibitor 1400W, the NADPH oxidase inhibitor apocynin, or in iNOS or p47 phox-deficient mice. These results correlated with the decreased expression of TNF-alpha and MCP-1. Kupffer cell depletion eliminated oxidative stress and inflammation, whereas in macrophage-depleted mice, the adoptive transfer of leptin-primed macrophages significantly restored inflammation.
conclusionsThese results, for the first time, suggest that leptin action in macrophages of the steatotic liver, through induction of iNOS and NADPH oxidase, causes peroxynitrite-mediated oxidative stress thus activating Kupffer cells.
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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.