{
  "abstract": "MAFLD is a global epidemic with a limited number of approved targeted therapies, underscoring the urgent need to define its underlying regulatory mechanisms. Here, we identify VGLL4 as a positive regulator of MAFLD progression. Hepatocyte-specific overexpression of Vgll4 induces hepatic steatosis, insulin resistance, and inflammation, whereas its knockout protects mice from HFD-induced metabolic dysfunction. Mechanistically, VGLL4 strengthens the interaction between TEAD4 and CEBPA and promotes the cooperative activation of Pdk4 expression. Functional studies identify PDK4 as a downstream effector, as its knockdown alleviates VGLL4-exacerbated hepatosteatosis in vivo. YAP attenuates this regulatory mechanism and suppresses Pdk4 transcription during hepatic steatosis. Notably, administration of Super-TDU, a peptide that disrupts the VGLL4–TEADs interaction, significantly alleviates hepatic steatosis in both HFD-fed mice and Vgll4-overexpressing mice. Our findings unveil the VGLL4–TEAD4/CEBPA–PDK4 axis as a key driver of MAFLD and demonstrate that its pharmacological blockade alleviates hepatic steatosis in model mice.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences",
    "Department of Urology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University",
    "Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences",
    "Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University",
    "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education",
    "School of Basic Medical Sciences, Dali University",
    "Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, University of Chinese Academy of Sciences",
    "Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People’s Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yixing Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaodong Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Wentao Yu"
    },
    {
      "affs": [
        3
      ],
      "name": "Meixi Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Jinjin Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hao Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Ruizeng Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoen Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoran Gao"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhuoqun Gao"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiayan Yan"
    },
    {
      "affs": [
        4
      ],
      "name": "Zhifeng Jiang"
    },
    {
      "affs": [
        4
      ],
      "name": "Shiyu Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Xueyan Ma"
    },
    {
      "affs": [
        3
      ],
      "name": "Jing Yu"
    },
    {
      "affs": [
        3
      ],
      "name": "Fang Wei"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiang Fu"
    },
    {
      "affs": [
        6
      ],
      "name": "Yi Zhou"
    },
    {
      "affs": [
        4
      ],
      "name": "Jian Zhou"
    },
    {
      "affs": [
        7
      ],
      "name": "Jian Wan"
    },
    {
      "affs": [
        3
      ],
      "name": "Yunyun Jin"
    },
    {
      "affs": [
        1
      ],
      "name": "Lei Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0caf9c56nf9e8.bib",
  "cited_by": 0,
  "doi": "10.1038/s44319-026-00934-x",
  "fulltext_url": "https://doi.org/10.1038/s44319-026-00934-x",
  "id": "0caf9c56nf9e8",
  "issns": [
    "1469-3178"
  ],
  "landing_url": "https://doi.org/10.1038/s44319-026-00934-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "lcc",
      "QH301-705.5"
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      "2713|Liver Disease Diagnosis and Treatment"
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  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44319-026-00934-x.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "Springer Nature",
  "ris": "https://research.draconitic.com/paper/0caf9c56nf9e8.ris",
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    {
      "first_seen": "2026-10-30T13:46:27Z",
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      "field": "medicine",
      "origin": "openalex:2713|Liver Disease Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
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  ],
  "title": "VGLL4 enhances PDK4 transcription and promotes metabolic dysfunction-associated fatty liver disease",
  "title_text": "VGLL4 enhances PDK4 transcription and promotes metabolic dysfunction-associated fatty liver disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:27Z",
  "url": "https://research.draconitic.com/paper/0caf9c56nf9e8",
  "venue": "EMBO Reports",
  "versions": []
}