{
  "abstract": "Tumor necrosis factor α-induced protein 3 (TNFAIP3) has been implicated in various liver diseases, but its role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. We analyzed TNFAIP3 expression in diet-induced MASLD mouse models using public transcriptomic data. In vitro, we investigated the effects of TNFAIP3 overexpression and knockdown in HepG2 cells on lipid accumulation, autophagy, and key metabolic pathways. In vivo, a high-fat diet-induced mouse model was used to validate the protective role of TNFAIP3. TNFAIP3 was consistently upregulated in the livers of various MASLD mouse. Overexpression of TNFAIP3 in HepG2 cells reduced lipid droplet accumulation, whereas knockdown aggravated lipid deposition. TNFAIP3 enhanced autophagy by stabilizing ATG4B, and this effect was autophagy-dependent. In vivo, TNFAIP3 overexpression alleviated hepatic steatosis, improved insulin sensitivity, and modulated lipid metabolism-associated pathways. These effects were reversed by autophagy inhibitors. Furthermore, TNFAIP3 upregulation was driven by NF-κB signaling, as inhibition of NF-κB decreased TNFAIP3 levels. The NF-κB-TNFAIP3 axis regulates hepatic lipid metabolism and protects against liver injury in MASLD, primarily through autophagy. These findings suggest that TNFAIP3 could serve as a potential therapeutic target for MASLD and other metabolic liver diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. dragonking1870@126.com.",
    "Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. guohui19820623@126.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qun Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Guixin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Huixiang Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangwei Liao"
    },
    {
      "affs": [
        1
      ],
      "name": "Long Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jinghui Guo",
      "orcid": "0000-0002-2609-4223"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/938pdmbq1m87w.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03310-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13720041",
  "id": "938pdmbq1m87w",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957644",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2713|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7204165010",
  "pdf_url": "https://europepmc.org/articles/PMC13720041?pdf=render",
  "pmcid": "PMC13720041",
  "pmid": "42957644",
  "published": "2026-08-25",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/938pdmbq1m87w.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:45Z",
      "native_id": "MED:42957644",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957644"
    },
    {
      "first_seen": "2026-11-02T12:23:54Z",
      "native_id": "PMC13720041",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03310-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Liver Disease Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "The NF-κB-TNFAIP3 axis attenuates MASLD via activation of hepatocyte autophagy.",
  "title_text": "The NF-κB-TNFAIP3 axis attenuates MASLD via activation of hepatocyte autophagy.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:00Z",
  "url": "https://research.draconitic.com/paper/938pdmbq1m87w",
  "venue": "Cell death discovery",
  "versions": []
}