{
  "abstract": "Obesity arises when a chronic energy surplus overwhelms the storage capacity of adipocytes and subsequently causes systemic metabolic dysfunction. Adaptive thermogenesis, primarily mediated by uncoupling protein 1 (Ucp1) in adipocytes, serves to counteract obesity by dissipating excess energy as heat. Despite extensive studies on thermogenic regulation, the phosphatases that regulate this protective metabolic pathway remain poorly understood. Here we identify dual-specificity phosphatase 4 (Dusp4) as a critical modulator of adipocyte thermogenesis via direct modulation of CREB-regulated transcription coactivator 3 (Crtc3). Dusp4-knockout mice exhibit impaired thermogenic capacity, diminished Ucp1 expression, and increased susceptibility to diet-induced obesity coupled with severe insulin resistance. Mechanistically, Dusp4 directly dephosphorylates serine residues on Crtc3, facilitating its nuclear translocation and subsequent transcriptional activation of Ucp1. Depot-targeted restoration of catalytically active Dusp4 in inguinal adipose tissue rescues local thermogenic gene expression and reinstates Crtc3 dephosphorylation-dependent Ucp1 induction in Dusp4-knockout mice. Collectively, these findings identify Dusp4 as a key upstream phosphatase orchestrating the Crtc3–Ucp1 thermogenic axis, and highlight its potential as a therapeutic target for obesity-associated metabolic disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea",
    "Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea",
    "Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, Republic of Korea",
    "School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea",
    "Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea",
    "Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Min Jeong Son"
    },
    {
      "affs": [
        0
      ],
      "name": "Hae Un Kook"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jaeeun Jung"
    },
    {
      "affs": [
        2
      ],
      "name": "Se-Jun Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Young Joo Jeon"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kyoung-Jin Oh",
      "orcid": "0000-0002-2224-7202"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Eun-Woo Lee",
      "orcid": "0000-0002-5156-0003"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Baek Soo Han"
    },
    {
      "affs": [
        5
      ],
      "name": "Jang Hyun Choi",
      "orcid": "0000-0003-0526-9028"
    },
    {
      "affs": [
        0
      ],
      "name": "Kwang-Hee Bae",
      "orcid": "0000-0002-5868-2556"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Won Kon Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0g1ygy8nbekpc.bib",
  "cited_by": 0,
  "doi": "10.1038/s12276-026-01850-9",
  "fulltext_url": "https://doi.org/10.1038/s12276-026-01850-9",
  "id": "0g1ygy8nbekpc",
  "issns": [
    "2092-6413",
    "1226-3613"
  ],
  "landing_url": "https://doi.org/10.1038/s12276-026-01850-9",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "lcc",
      "QD415-436"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2737|Adipose Tissue and Metabolism"
    ]
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  "openalex": "W7215998177",
  "pdf_url": "https://www.nature.com/articles/s12276-026-01850-9.pdf",
  "pmcid": "PMC13737205",
  "pmid": "42827111",
  "published": "2026-10-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/0g1ygy8nbekpc.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T14:20:55Z",
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      "url": "https://doi.org/10.1038/s12276-026-01850-9"
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    {
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Adipose Tissue and Metabolism",
      "subfield": "physiology"
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  ],
  "title": "DUSP4 activates adipocyte thermogenesis via CRTC3 dephosphorylation-dependent UCP1 expression",
  "title_text": "DUSP4 activates adipocyte thermogenesis via CRTC3 dephosphorylation-dependent UCP1 expression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T14:21:15Z",
  "url": "https://research.draconitic.com/paper/0g1ygy8nbekpc",
  "venue": "Experimental and Molecular Medicine",
  "versions": []
}