{
  "abstract": "Obesity is a global health challenge increasingly linked to environmental obesogens. Tributyltin (TBT), a model obesogen that activates PPARγ and RXR, promotes transgenerational obesity in mice, but whether developmental and ancestral exposure impairs energy balance remains unclear. Brown adipose tissue (BAT) contributes to energy expenditure and thermoregulation through UCP1-dependent and -independent pathways. We tested whether TBT exposure disrupts BAT function in F1 and F3 descendants of exposed F0 dams.\n\nWe measured body composition before and after high-fat diet (HFD) challenge and assessed resting core body temperature, BAT gene expression, mitochondrial DNA (mtDNA) content, and mitochondrial electron transport chain (ETC) capacity. TBT-line males accumulated more fat after HFD without changes in lean mass despite similar mass-scaled food intake. Before HFD, core body temperature was lower in F1 and F3 TBT-line males, indicating impaired thermal homeostasis before increased adiposity. Candidate-gene qPCR did not show uniform suppression of thermogenic genes; instead, Ucp1 mRNA increased while Ucp2 mRNA decreased in F1 males, indicating dysregulation. Transcriptomal profiling revealed altered thermogenic signaling and consistent downregulation of mitochondrial electron transport chain genes across F1 and F3 males. Relative mtDNA content was unchanged, whereas complex-specific respirometry revealed reduced complex I- and II-associated respiratory capacity, providing evidence of impaired electron transport. No consistent effects occurred in females.\n\nThese findings identified an early, male-associated BAT phenotype characterized by thermogenic dysregulation, reduced mitochondrial ETC capacity, and impaired thermal homeostasis. They support a model in which impaired BAT mitochondrial function contributes to later susceptibility to diet-induced adiposity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Developmental and Cell Biology, University of California, Irvine, CA, USA, 92697-2300",
    "Krantz Family Center for Cancer Research, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA, 02129, USA",
    "Department of Biomedical Engineering, University of California, Irvine, CA, USA, 92697-2300"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yikai Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Richard C. Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Katelyn Uyen Nguyen"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaitlin To"
    },
    {
      "affs": [
        0
      ],
      "name": "Myah Gibbs"
    },
    {
      "affs": [
        1
      ],
      "name": "Harunori Honjoh",
      "orcid": "0009-0004-3953-6010"
    },
    {
      "affs": [
        1
      ],
      "name": "Toshi Shioda",
      "orcid": "0000-0002-9434-7835"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Bruce Blumberg",
      "orcid": "0000-0002-8016-8414"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/11p6mm4vvvpxx.bib",
  "cited_by": 0,
  "doi": "10.1101/2025.11.04.686561",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733718/",
  "id": "11p6mm4vvvpxx",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://doi.org/10.1101/2025.11.04.686561",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2737|Adipose Tissue and Metabolism"
    ]
  ],
  "openalex": "W4415936980",
  "pdf_url": null,
  "pmcid": "PMC13733718",
  "pmid": "42990175",
  "published": "2026-10-27",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/11p6mm4vvvpxx.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:26Z",
      "native_id": "PMC13733718",
      "source": "pmc",
      "url": "https://doi.org/10.1101/2025.11.04.686561"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Adipose Tissue and Metabolism",
      "subfield": "physiology"
    }
  ],
  "title": "Ancestral Tributyltin Exposure Produces Male-Specific Brown Adipose Thermogenic Dysregulation",
  "title_text": "Ancestral Tributyltin Exposure Produces Male-Specific Brown Adipose Thermogenic Dysregulation",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:26Z",
  "url": "https://research.draconitic.com/paper/11p6mm4vvvpxx",
  "venue": "bioRxiv",
  "versions": []
}