{
  "abstract": "Background\n\nMetabolically healthy obesity and metabolically unhealthy obesity may occupy different positions along a continuum of adipose-tissue dysfunction, but stable molecular distinctions remain uncertain.Methods\n\nWe integrated three public human subcutaneous-adipose-tissue transcriptomic datasets while preserving participant and platform independence. GSE244118 was used for discovery, GSE152991 was restricted to 14 participants not overlapping with the discovery cohort, and GSE55200 provided cross-platform supportive evidence. We performed differential-expression analysis, correlation-adjusted Reactome testing, direction-aware cross-dataset integration, discovery-defined module scoring, and adipose-tissue deconvolution.Results\n\nFifty genes met conventional thresholds for metabolically unhealthy versus metabolically healthy obesity in the discovery dataset, but none passed the prespecified fold-change-aware test or strict cross-dataset replication. Among 1570 shared Reactome pathways, 409 reached false-discovery rate < 0.05 in signed-Z integration and 387 had concordant directions across all datasets. Metabolically unhealthy obesity consistently showed lower mitochondrial translation, respiratory-chain, and energy-metabolism programs, accompanied by secondary increases in extracellular-matrix remodeling. A discovery-defined mitochondrial module was lower in metabolically unhealthy obesity in synthesis restricted to non-discovery datasets under both rank and z-mean scoring. The 14-person holdout alone did not establish a significant module difference, and the extracellular-matrix module synthesis was nonsignificant. Ordered cross-sectional patterns and composition sensitivity described tissue-level associations.Conclusions\n\nMetabolic obesity heterogeneity was therefore more reproducible at pathway and module levels than at the single-gene level. Unresolved clinical confounding and bulk tissue composition limit functional and causal interpretation.",
  "abstract_shown": true,
  "affiliations": [
    "School of Kinesiology and Health, Capital University of Physical Education and Sports, Beijing 100191, China.",
    "Division of Sports Science and Physical Education, Tsinghua University, Beijing 100084, China.",
    "College of Forestry, Beijing Forestry University, Beijing 100083, China.",
    "Beijing Institute of Nutritional Resources Company Limited, Beijing 100069, China.",
    "Central Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuang Bai",
      "orcid": "0000-0003-3930-9227"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Meng Qi",
      "orcid": "0000-0003-0738-2454"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuang Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Junzhu Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Qing Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yajuan Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyuan Ma"
    },
    {
      "affs": [
        4
      ],
      "name": "Dongling Wang",
      "orcid": "0009-0005-5520-7791"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eabjgs4fkhfgg.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101199",
  "fulltext_url": "https://europepmc.org/articles/PMC13704403",
  "id": "eabjgs4fkhfgg",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938315",
  "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",
      "2713|Adipokines, Inflammation, and Metabolic Diseases"
    ]
  ],
  "openalex": "W7214584283",
  "pdf_url": "https://europepmc.org/articles/PMC13704403?pdf=render",
  "pmcid": "PMC13704403",
  "pmid": "42938315",
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eabjgs4fkhfgg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42938315",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938315"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Adipokines, Inflammation, and Metabolic Diseases",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.",
  "title_text": "Human Subcutaneous Adipose Transcriptomes Link Mitochondrial Transcription to Metabolic Heterogeneity in Obesity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/eabjgs4fkhfgg",
  "venue": "Genes",
  "versions": []
}