{
  "abstract": "While glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide are effective in treating obesity, up to 45% of the resulting weight loss can be attributed to skeletal muscle loss. Given the critical role of skeletal muscle in health and mobility, this may have long-term adverse consequences. Herein we investigated whether oral ketone ester supplementation could prevent semaglutide-induced muscle loss and explored the underlying molecular mechanisms. Obese, glucose-intolerant mice received vehicle, semaglutide, or semaglutide plus a β-hydroxybutyrate-generating ketone ester for 3 weeks. Body composition, muscle strength, and endurance were assessed longitudinally. Semaglutide monotherapy reduced lean mass, impaired muscle strength, and suppressed mitochondrial gene expression while elevating atrophy-related genes in skeletal muscle samples. Co-administration with ketone ester preserved skeletal muscle mass and function without compromising fat loss. Mechanistically, ketone ester cotreatment prevented semaglutide-induced changes in mitochondrial and atrophy-related gene expression, suggesting that mitochondrial defects and impaired ketone metabolism contribute to GLP-1RA-induced muscle loss. Together, these findings demonstrate that ketone ester supplementation can maintain muscle mass and performance during semaglutide-driven weight loss. These preclinical findings support ketone therapy as a promising strategy to counteract the sarcopenia-promoting effects of GLP-1RAs and warrant clinical evaluation to assess its translational potential.",
  "abstract_shown": true,
  "affiliations": [
    "Alberta Diabetes Institute,",
    "Cardiovascular Research Centre,",
    "Department of Pediatrics,",
    "Women and Children’s Health Research Institute,",
    "Department of Biochemistry, Faculty of Medicine & Dentistry, and",
    "Faculty Saint-Jean, University of Alberta, Edmonton, Alberta, Canada"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yasser Abuetabh"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Mya A Schmidt",
      "orcid": "0009-0009-6872-5589"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Masaaki Naganuma",
      "orcid": "0000-0001-6084-8669"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ramana Vaka"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Mahmoud A. El‐Ghiaty",
      "orcid": "0000-0003-2900-7129"
    },
    {
      "affs": [
        4
      ],
      "name": "Shelly Braun",
      "orcid": "0009-0000-5706-1988"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ethan D. Kwan",
      "orcid": "0000-0002-5912-3502"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Matthieu C P Zolondek"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Darius Sahid"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Laibah Khan"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Rajat K. Shandal"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ashley L. Trudeau"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yaning Li"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Sufyan O. Malik"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Qiuyu Sun"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Danica K. Roth"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Daniela Y. Morales-Llamas"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jody L. Levasseur",
      "orcid": "0009-0003-3040-2449"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Mourad Ferdaoussi",
      "orcid": "0000-0001-7636-0959"
    },
    {
      "affs": [
        4
      ],
      "name": "Richard P. Fahlman",
      "orcid": "0000-0003-4104-6374"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jason R.B. Dyck",
      "orcid": "0000-0002-7045-2884"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/akan4bqb3edqf.bib",
  "cited_by": 8,
  "doi": "10.1172/jci.insight.201810",
  "fulltext_url": null,
  "id": "akan4bqb3edqf",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.201810",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7164010090",
  "pdf_url": "http://insight.jci.org/articles/view/201810/files/pdf",
  "pmcid": "PMC13464422",
  "pmid": "42262870",
  "published": "2026-06-09",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/akan4bqb3edqf.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T13:20:45Z",
      "native_id": "W7164010090",
      "source": "openalex",
      "url": "https://doi.org/10.1172/jci.insight.201810"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Semaglutide-induced loss of skeletal muscle mass is blunted by co-administration of ketone esters",
  "title_text": "Semaglutide-induced loss of skeletal muscle mass is blunted by co-administration of ketone esters",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/akan4bqb3edqf",
  "venue": "JCI Insight",
  "versions": []
}