{
  "abstract": "Background\n\nLiver inflammation and fibrosis are reparative responses to chronic liver injury. Bone marrow-derived monocyte/macrophages (BMDMs) are key participants. Our previous study demonstrated that BMDM can be activated as a proinflammatory phenotype by sphingosine-1-phosphate (S1P). Aconitate decarboxylase 1 (ACOD1)/itaconate is an anti-inflammatory molecule. However, it remains unclear whether ACOD1/itaconate is involved in S1P-induced BMDM activation.Methods\n\nA methionine-choline-deficient and high-fat diet was used to induce liver injury and fibrosis in mice. To clarify the role of endogenous ACOD1/itaconate in BMDMs in liver fibrosis, we established 2 types of chimeric mice: (1) bone marrow (BM) Acod1 deficiency (WT or Acod1 knockout BM was transplanted into wild-type mice) and (2) exclusive BM Acod1 expression (WT or Acod1 knockout BM was transplanted into Acod1 knockout mice).Results\n\nSingle-cell RNA sequencing data revealed that Acod1 was highly expressed in injured BMDMs. Acod1+ BMDMs exhibited a proinflammatory phenotype with elevated expression of proinflammatory genes. In vitro, ACOD1 expression and itaconate production were upregulated in S1P-treated BMDMs. Endogenous ACOD1/itaconate in BMDMs suppressed BMDM proinflammatory activation by forming negative feedback with NF-κB signaling. S1P-regulated ACOD1 expression and BMDM activation via the same signaling pathway (S1PR2/MAPK/NF-κB signaling), indicating the endogenous brake function of ACOD1/itaconate. In chimeric mice with BM Acod1 deficiency, the abolition of the endogenous brake function of ACOD1/itaconate aggravated liver inflammation/fibrosis. Exclusive BM Acod1 expression showed the opposite effects.Conclusions\n\nACOD1/itaconate exerts an endogenous brake function in the proinflammatory activation of BMDMs during chronic liver injury. Our data demonstrate the role of ACOD1/itaconate in S1P-induced BMDM activation, further indicating that ACOD1/itaconate is a potential therapeutic strategy for liver inflammation/fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory for Clinical Medicine, Department of Cell Biology, Capital Medical University, Beijing, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kai Zhang"
    },
    {
      "name": "Tong Li"
    },
    {
      "name": "Wenhui Liu"
    },
    {
      "name": "Weiyang Li"
    },
    {
      "name": "Lin Yang"
    },
    {
      "name": "Na Chang"
    },
    {
      "name": "Liying Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2hzkc1wes970f.bib",
  "cited_by": 0,
  "doi": "10.1097/hc9.0000000000001034",
  "fulltext_url": "https://europepmc.org/articles/PMC13682833",
  "id": "2hzkc1wes970f",
  "issns": [
    "2471-254X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42900160",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7223092222",
  "pdf_url": "https://europepmc.org/articles/PMC13682833?pdf=render",
  "pmcid": "PMC13682833",
  "pmid": "42900160",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2hzkc1wes970f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42900160",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42900160"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Itaconate as the endogenous brake of proinflammatory macrophage activation alleviates inflammation in liver fibrogenesis.",
  "title_text": "Itaconate as the endogenous brake of proinflammatory macrophage activation alleviates inflammation in liver fibrogenesis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/2hzkc1wes970f",
  "venue": "Hepatology communications",
  "versions": []
}