ArticleJournal of lipid research2018
Oxidized linoleic acid metabolites induce liver mitochondrial dysfunction, apoptosis, and NLRP3 activation in mice.
Article in Journal of lipid research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 90 citations in OpenAlex.
- Mitochondrial Dysfunction in Metabolic-Syndrome-Related MASLD/MASH: Metabolic Mechanisms and Therapeutic Perspectives.Metabolites · 2026Review
- Label-free 4D holotomography with depth-adaptive segmentation for quantitative analysis of lipid droplet dynamics in hepatic organoids.Biophotonics discovery · 2026Article
- Urinary extracellular vesicles levels of n-3 and n-6 polyunsaturated fatty acids in children with steroid-sensitive nephrotic syndrome: a pilot study.BMC nephrology · 2026Article
- P2-HNF4α alters linoleic acid metabolism and mitigates soybean oil-induced obesity: role for oxylipins.Journal of lipid research · 2025Article
- Historical rise of cancer and dietary linoleic acid: Mechanisms and therapeutic strategies.World journal of clinical oncology · 2025Review
- Disrupting lipid homeostasis with CAV2 in OSCC triggers apoptosis, lipolysis, and mitochondrial dysfunction by transcriptional repression of PPARγ.Cell & bioscience · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Efficacy and mechanism of action of harmine derivative H-2-104 against Echinococcus granulosus infection in mice.BMC veterinary research · 2025Article
- Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- The controversial role of linoleic acid in cardiometabolic health: from molecular pathways to human studies.Frontiers in nutrition · 2025Review
- The energy model of insulin resistance: A unifying theory linking seed oils to metabolic disease and cancer.Frontiers in nutrition · 2025Article
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.Animal models and experimental medicine · 2025Article
- Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation.EBioMedicine · 2024Review
- Hepatic oxylipin profiles in mouse models of Wilson disease: New insights into early hepatic manifestations.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro.Prostaglandins, leukotrienes, and essential fatty acids · 2024Article
- The metabolomics changes in epididymal lumen fluid of CABS1 deficient male mice potentially contribute to sperm deformity.Frontiers in endocrinology · 2024Article
- Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications.Arquivos brasileiros de cardiologia · 2023Article
- Vitamin E Induces Liver Iron Depletion and Alters Iron Regulation in Mice.The Journal of nutrition · 2023Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Circulating oxidized linoleic acid (LA) metabolites (OXLAMs) are increased in patients with nonalcoholic steatohepatitis (NASH) and their levels correlate with disease severity. However, the mechanisms by which OXLAMs contribute to NASH development are incompletely understood. We tested the hypothesis that LA or OXLAMs provided directly through the diet are involved in the development of hepatic injury. C57BL/6 mice were fed an isocaloric high-fat diet containing low LA, high LA, or OXLAMs for 8 weeks. The livers of OXLAM-fed mice showed lower triglyceride concentrations, but higher FA oxidation and lipid peroxidation in association with increased oxidative stress. OXLAM-induced mitochondrial dysfunction was associated with reduced Complex I protein and hepatic ATP levels, as well as increased mitochondrial biogenesis and cytoplasmic mitochondrial DNA. Oxidative stress increased thioredoxin-interacting protein (TXNIP) in the liver and stimulated the activation of mitochondrial apoptosis signal-regulating kinase 1 (ASK1) leading to apoptosis. We also found increased levels of NOD-like receptor protein 3 (NLRP3) inflammasome components and Caspase-1 activation in the livers of OXLAM-fed mice. In vitro, OXLAMs induced hepatocyte cell death, which was partly dependent on Caspase-1 activation. This study identified key mechanisms by which dietary OXLAMs contribute to NASH development, including mitochondrial dysfunction, hepatocyte cell death, and NLRP3 inflammasome activation.
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