{
  "abstract": "Obesity and metabolic diseases such as diabetes reflect long-term interactions between diet, lifestyle, and genetics, variables that are hard to control in humans but can be systematically varied in mice, though behavioral variables like long-term exercise remain harder to model. Having previously phenotyped ~50 BXD strains, we identified BXD40, BXD43, and BXD100 as predisposed to voluntary wheel-running (~6 km/day at 24 weeks) with variable susceptibility to diet-induced obesity and diabetes. We followed these strains from 8-32 weeks on a 60% kcal/fat high-fat (HF) diet, with or without access to running wheels. Wheel usage declined from ~9 km/day in the first two weeks to a steady ~5 km/day thereafter yet still improved oral glucose tolerance by 35% over sedentary controls by 24 weeks. Despite equivalent body weight, runners ate 20% more relative to body weight, indicating the glucose benefit was independent of caloric intake. We next asked whether the gut microbiome contributes to this benefit. Long-term exercise produced only modest, cohort-dependent shifts in cecal microbial composition, though functional profiling revealed exercise-associated differences in carbohydrate- and glucose-metabolism pathways. Reciprocal bedding exchange between sedentary and running BXD43 cages reduced microbial differentiation in a taxon-specific manner and coincided with marked attenuation of the glucose phenotype, despite unchanged running behavior. Together, these findings validate BXD40, BXD43, and BXD100, alongside the canonical C57BL/6, as a model for studying diet, exercise, and genetics in metabolic disease, and implicate gut microbial taxa in shaping exercise's metabolic effects during HF feeding.",
  "abstract_shown": true,
  "affiliations": [
    "University of Luxembourg"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "A. Lamanna"
    },
    {
      "name": "Z. Zhou"
    },
    {
      "name": "B. Boussoufa"
    },
    {
      "name": "E. Pansart"
    },
    {
      "name": "M. Buttini"
    },
    {
      "name": "T. Heurtaux"
    },
    {
      "name": "P. Garcia"
    },
    {
      "name": "G. Marcon"
    },
    {
      "name": "D. Coowar"
    },
    {
      "affs": [
        0
      ],
      "name": "E. G. Williams"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d8rfc9f7qvr3q.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.752290",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.752290v1.full",
  "id": "d8rfc9f7qvr3q",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.752290v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "1312|Gut microbiota and health"
    ]
  ],
  "openalex": "W7216384364",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.752290v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d8rfc9f7qvr3q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:51Z",
      "native_id": "10.64898/2026.09.28.752290",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.752290v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Voluntary Exercise Differentially Affects High-Fat Induced Metabolic Phenotypes Across BXD Mouse Strains",
  "title_text": "Voluntary Exercise Differentially Affects High-Fat Induced Metabolic Phenotypes Across BXD Mouse Strains",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:51Z",
  "url": "https://research.draconitic.com/paper/d8rfc9f7qvr3q",
  "venue": "bioRxiv",
  "versions": []
}