{
  "abstract": "Obesity is linked to complex interactions between an organism’s genetic background and its environment. Mouse models have been invaluable research tools to study obesity, with C57BL/6N being widely studied, given its propensity for weight gain on a high-fat diet (HFD). Despite this, the genetic basis of its susceptibility is poorly understood. In a partner paper we have identified SNP variants in 11 genes causing susceptibility to, or protection against, HFD-induced obesity in male C57BL/6N mice explaining 87% of the individual variation in fat gain. Surprisingly, most of them were maximally expressed outside the brain. In this study, we further validate some of these targets. We demonstrate that tissue-specific inhibition of Nova1 and Mchr1 in muscle, Nr1i3 in liver, and Ahr in lung and liver led to resistance to HFD–induced obesity or glucose intolerance. Further RNAseq analysis revealed that mTOR, Acox1, IL-15, and eIF2a signals are positioned downstream of these genes, potentially mediating their effects on obesity susceptibility. Importantly, variants in eight of the genes identified here have been previously implicated in human obesity, suggesting that a deeper understanding of the genetic/environment interactions of model systems can inform this complex human disease. Our work confirms that body fat regulation is likely more complex than current models which focus on the brain–adipose axis suggest.",
  "abstract_shown": true,
  "affiliations": [
    "Institutes of Biomedical Sciences, Inner Mongolia University, Hohhot 010020, China",
    "Laboratory of Integrative Physiology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China",
    "Faculty of Space Technologies, Akademia Gorniczo-Hutnicza, University of Krakow, Krakow 30-059, Poland",
    "Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai 264005, China",
    "Department of Clinical Nutrition, Peking University Third Hospital, Beijing, China",
    "Institute of Health Sciences, China Medical University, Shenyang, Liaoning 110122, China",
    "Shenzhen Key laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China",
    "Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, Scotland, United Kingdom",
    "Faculty of Pharmaceutical Sciences Shenzhen, Shenzhen University of Advanced Technology, Shenzhen 518107, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yingga Wu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Agata M. Rudolf"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Lu Wang",
      "orcid": "0000-0002-1654-3259"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Zhengjie Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Chaoqun Niu"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Fan Xia"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Anyongqi Wang"
    },
    {
      "affs": [
        7
      ],
      "name": "Sharon E. Mitchell",
      "orcid": "0000-0003-3941-0309"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoran Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yalin He"
    },
    {
      "affs": [
        1
      ],
      "name": "Chunyu Chen"
    },
    {
      "affs": [
        1,
        6,
        7,
        8
      ],
      "name": "John R. Speakman",
      "orcid": "0000-0002-2457-1823"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1xd46wbsdgqy2.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2613776123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715730/",
  "id": "1xd46wbsdgqy2",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2613776123",
  "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",
      "422"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Medical Sciences"
    ],
    [
      "openalex",
      "2807|Regulation of Appetite and Obesity"
    ]
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  "openalex": "W7223112862",
  "pdf_url": "https://www.pnas.org/doi/pdf/10.1073/pnas.2613776123",
  "pmcid": "PMC13715730",
  "pmid": "42905550",
  "published": "2026-10-21",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/1xd46wbsdgqy2.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:57Z",
      "native_id": "PMC13715730",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2613776123"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Regulation of Appetite and Obesity",
      "subfield": "physiology"
    }
  ],
  "title": "Validation of targets linked to weight gain in C57BL/6 mice and translational aspects in humans",
  "title_text": "Validation of targets linked to weight gain in C57BL/6 mice and translational aspects in humans",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:57Z",
  "url": "https://research.draconitic.com/paper/1xd46wbsdgqy2",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}