{
  "abstract": "The Gly482Ser SNP (rs8192678) in the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene has been associated with obesity, type 2 diabetes and other human metabolic diseases. In this study, we found that human iPSCs carrying a serine risk allele had reduced respiratory capacity, and individuals living with overweight or obesity homozygous for the serine allele (S/S) exhibited a preference for carbohydrate oxidation following a high-fat meal. Using a PGC-1Ser481Gly knock-in mouse model, we performed metabolic phenotyping of male and female mice carrying the three genotypes (G/G, S/G, S/S) under acute nutritional challenges (chow, fasting and high-fat high-sugar (HFHS) feeding) and chronic HFHS feeding. S/S females were heavier and showed a trend toward an increased respiratory exchange ratio (RER) during fasting, with greater weight gain and fat mass following chronic HFHS feeding. Transcriptomic analyses revealed tissue-specific reprogramming of mitochondrial oxidative pathways, that were downregulated in subcutaneous adipose tissue and liver while upregulated in muscle, with the strongest effects observed in S/S females. Together, these findings provide in vivo evidence that this SNP reprograms whole-body oxidative metabolism, with a net effect of favoring carbohydrate oxidation and energy conservation, particularly in females.",
  "abstract_shown": true,
  "affiliations": [
    "IRCM"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "M. Galipeau"
    },
    {
      "name": "N. Jouvet"
    },
    {
      "name": "M. Schoumacher"
    },
    {
      "name": "E. Courty"
    },
    {
      "name": "R. Vandenbeek"
    },
    {
      "name": "A. Gunes"
    },
    {
      "name": "M. Braud"
    },
    {
      "name": "C. Fourgeux"
    },
    {
      "name": "J. Poschmann"
    },
    {
      "name": "F. C. Lynn"
    },
    {
      "name": "M. Faraj"
    },
    {
      "affs": [
        0
      ],
      "name": "J. L. Estall"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/79gay21c8rp7p.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.759626",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759626v1.full",
  "id": "79gay21c8rp7p",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759626v1",
  "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",
      "physiology"
    ],
    [
      "openalex",
      "2737|Adipose Tissue and Metabolism"
    ]
  ],
  "openalex": "W7223209830",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759626v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/79gay21c8rp7p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:12Z",
      "native_id": "10.64898/2026.10.16.759626",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759626v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "The PGC-1α Gly482Ser rs8192678 SNP reprograms oxidative metabolism to favor energy storage in females",
  "title_text": "The PGC-1α Gly482Ser rs8192678 SNP reprograms oxidative metabolism to favor energy storage in females",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:12Z",
  "url": "https://research.draconitic.com/paper/79gay21c8rp7p",
  "venue": "bioRxiv",
  "versions": []
}