{
  "abstract": "Male obesity negative affects gametic function and offspring metabolism. We here describe that (F₀) obesity and weight loss in male mice reversibly alter metabolism and impair adipose mitochondrial function. These metabolic aberrations are transmitted to male offsprings (F₁), which display reduced mitochondrial gene expression. Mechanistically, we identify microRNAs let-7d/ e as epigenetic mediators induced in obese F₀ sperm and in F₀/F₁ adipose tissue, where they silence the miRNA processor DICER1 and impair mitochondrial activity. Microinjecting let-7d/e into lean zygotes phenocopies the paternal obesity phenotype, inducing glucose intolerance and mitochondrial gene suppression in sired offspring. Single-cell RNA sequencing of blastomeres reveals that let-7d/e impair oxidative metabolism in early embryos. Furthermore, lifestyle-induced weight loss in males with obesity downregulates human HSA-LET-7D/E in semen, indicating a conserved role for let-7 in transmission of metabolic health. These findings demonstrate that micro-RNA let-7 in sperm reprograms offspring metabolism by modulating mitochondrial function during early development.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 36,
  "authors": [
    {
      "name": "Chien Huang"
    },
    {
      "name": "Joo-Hyun Park"
    },
    {
      "name": "Ali Altıntaş"
    },
    {
      "name": "Natasa Stanic"
    },
    {
      "name": "Kristine Kyle de Leon"
    },
    {
      "name": "Signe Isacson"
    },
    {
      "name": "Panagiotis Kalogeropoulos"
    },
    {
      "name": "Hande Topel"
    },
    {
      "name": "Tobias Madsen"
    },
    {
      "name": "Sebastian Zanner"
    },
    {
      "name": "Phillip Mm Ruppert"
    },
    {
      "name": "Rocio Valdebenito"
    },
    {
      "name": "Jesper Havelund"
    },
    {
      "name": "Bjørk Ditlev Marcher Larsen"
    },
    {
      "name": "Yen-Ting Chien"
    },
    {
      "name": "Wen-Chi Huang"
    },
    {
      "name": "Yovita Permata Budi"
    },
    {
      "name": "Yi-Fan Jiang"
    },
    {
      "name": "Andréa Livia Rocha"
    },
    {
      "name": "Niedson Correia Lima-Junior"
    },
    {
      "name": "Karolina Szczepanowska"
    },
    {
      "name": "Jan-Wilm Lackmann"
    },
    {
      "name": "Aleksandra Trifunovic"
    },
    {
      "name": "Eva Kildall Hejbøl"
    },
    {
      "name": "Sönke Detlefsen"
    },
    {
      "name": "Ida Engberg Jepsen"
    },
    {
      "name": "Stefanie Hansborg Kolstrup"
    },
    {
      "name": "Ricardo Laguna-Barraza"
    },
    {
      "name": "Javier Martin-Gonzalez"
    },
    {
      "name": "Konstantin Khodosevich"
    },
    {
      "name": "Nils J Færgeman"
    },
    {
      "name": "Marcelo A Mori"
    },
    {
      "name": "Marc R Friedländer"
    },
    {
      "name": "Anita Öst"
    },
    {
      "name": "Romain Barrès"
    },
    {
      "name": "Jan-Wilhelm Kornfeld"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mrqy8a9mphqw.bib",
  "cited_by": 5,
  "doi": "10.1038/s41467-026-69686-5",
  "fulltext_url": null,
  "id": "4mrqy8a9mphqw",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.science/hal-05849825v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bc"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.bc.bc"
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      "hal",
      "2.sdv.mhep.em"
    ],
    [
      "openalex",
      "2743|Sperm and Testicular Function"
    ]
  ],
  "openalex": "W7131240037",
  "pdf_url": "https://hal.science/hal-05849825/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/4mrqy8a9mphqw.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:51Z",
      "native_id": "hal-05849825",
      "source": "hal",
      "url": "https://hal.science/hal-05849825v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.em",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Male obesity causes adipose mitochondrial dysfunction in F1 mouse progeny via a let-7-DICER axis",
  "title_text": "Male obesity causes adipose mitochondrial dysfunction in F1 mouse progeny via a let-7-DICER axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:12Z",
  "url": "https://research.draconitic.com/paper/4mrqy8a9mphqw",
  "venue": "Nature Communications",
  "versions": []
}