{
  "abstract": "Graphical abstract\n\nAbstract\n\nObesity and diabetes arise from disrupted energy homeostasis, underscoring the need to identify mechanisms that enhance energy expenditure. Brown adipose tissue dissipates energy through mitochondria-dependent non-shivering thermogenesis; however, the transcriptional regulators coordinating this process remain incompletely defined. Here, we investigated the role of activating transcription factor 5 in thermogenic programming and mitochondrial metabolism in brown adipocytes using in vivo and in vitro models. Cold exposure and β3-adrenergic stimulation induced activating transcription factor 5 expression in brown adipose tissue and differentiated adipocytes, accompanied by activation of thermogenic gene programs. Mechanistically, activating transcription factor 5 functioned downstream of a nuclear protein kinase A-extracellular signal-regulated kinase pathway, whose nuclear activation was required for its induction and for upregulation of uncoupling protein 1. Loss of activating transcription factor 5 impaired thermogenic gene expression, reduced mitochondrial stress response and lipolytic programs, diminished mitochondrial oxidative capacity, and suppressed fatty acid oxidation, including reduced incorporation of fatty acid-derived carbons into the tricarboxylic acid cycle. Transcriptomic analysis revealed coordinated repression of pathways related to fatty acid oxidation, oxidative phosphorylation, and thermogenesis in activating transcription factor 5-deficient adipocytes. Live-cell imaging further confirmed that β3-adrenergic stimulation selectively enhanced nuclear kinase activity, establishing a nuclear-localized signaling axis. Together, these findings identify activating transcription factor 5 as a key transcriptional regulator linking mitochondrial metabolism and thermogenic gene expression, supporting its potential as a therapeutic target for enhancing energy expenditure in metabolic disease.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine , Daejeon, Republic of Korea.",
    "Department of Medical Science, Chungnam National University School of Medicine , Daejeon, Republic of Korea.",
    "Department of Life Sciences, Gwangju Institute of Science and Technology , Gwangju, Republic of Korea.",
    "Integrated Institute of Biomedical Research, Gwangju Institute of Science and Technology , Gwangju, Republic of Korea.",
    "Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P.R. China.",
    "Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University , Seoul, Republic of Korea.",
    "Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon, Republic of Korea.",
    "Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology , Daejeon, Republic of Korea.",
    "Department of Internal Medicine, Chungnam National University School of Medicine , Daejeon, Republic of Korea."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hyo Ju Jang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yeongjun Suh"
    },
    {
      "affs": [
        4
      ],
      "name": "Jingwen Tian"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ho Yeop Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Ji Sun Moon"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ha Thi Nga"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thi Linh Nguyen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alfin Mohammad Abdillah"
    },
    {
      "affs": [
        5
      ],
      "name": "Gyu Min Lim"
    },
    {
      "affs": [
        5
      ],
      "name": "Dong Wook Choi"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Chuna Kim"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yonghoon Kwon"
    },
    {
      "affs": [
        0,
        1,
        8
      ],
      "name": "Hyon-Seung Yi",
      "orcid": "0000-0002-3767-1954"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7ff7kaensn0ms.bib",
  "cited_by": 0,
  "doi": "10.1530/joe-26-0101",
  "fulltext_url": "https://europepmc.org/articles/PMC13695427",
  "id": "7ff7kaensn0ms",
  "issns": [
    "0022-0795",
    "1479-6805"
  ],
  "landing_url": "https://europepmc.org/article/MED/42847123",
  "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": [
    [
      "openalex",
      "2737|Adipose Tissue and Metabolism"
    ]
  ],
  "openalex": "W7220919366",
  "pdf_url": "https://europepmc.org/articles/PMC13695427?pdf=render",
  "pmcid": "PMC13695427",
  "pmid": "42847123",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7ff7kaensn0ms.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42847123",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42847123"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Adipose Tissue and Metabolism",
      "subfield": "physiology"
    }
  ],
  "title": "A nuclear ERK-ATF5 axis coordinates mitochondrial metabolism and thermogenic gene expression in brown adipocytes.",
  "title_text": "A nuclear ERK-ATF5 axis coordinates mitochondrial metabolism and thermogenic gene expression in brown adipocytes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/7ff7kaensn0ms",
  "venue": "The Journal of endocrinology",
  "versions": []
}