{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:51:53Z","timestamp":1793346713766,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["FS 167280"],"award-info":[{"award-number":["FS 167280"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>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 \u03b2-hydroxybutyrate\u2013generating 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\u2013induced 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.<\/jats:p>\n                  <jats:p>Ketone ester supplementation protects against muscle loss during semaglutide treatment without compromising fat reduction, offering a potential strategy to improve GLP-1 therapy outcomes.<\/jats:p>","DOI":"10.1172\/jci.insight.201810","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:00:18Z","timestamp":1781020818000},"source":"Crossref","is-referenced-by-count":8,"title":["Semaglutide-induced loss of skeletal muscle mass is blunted by co-administration of ketone esters"],"prefix":"10.1172","volume":"11","author":[{"given":"Yasser","family":"Abuetabh","sequence":"first","affiliation":[{"name":"Cardiovascular Research Centre,"},{"name":"Alberta Diabetes Institute,"},{"name":"Women and Children\u2019s Health 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