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The ketone body 3-hydroxybutyrate (3HB) serves as an alternative energy substrate and signaling molecule that modulates organelle function and myogenic programs. This study investigated how extracellular metabolic conditions and 3HB regulate autophagy-linked organelle remodeling in human external urethral sphincter (hEUS) myoblasts. Immortalized hEUS myoblasts (US2-KD) were differentiated under four conditions combining high-glucose Dulbecco\u2019s modified Eagle\u2019s medium (HG-DMEM) or low-glucose physiologically formulated minimum essential medium (LG-MEM) with or without 3HB. Metabolomic profiling revealed that the medium composition predominantly shaped energy and amino acid pathways, whereas 3HB induced subtler, context-dependent shifts in metabolites related to autophagy and mitochondrial function. At the cellular level, LG-MEM accelerated myogenic differentiation compared to HG-DMEM, with earlier induction of\n                    <jats:italic>MYOG<\/jats:italic>\n                    and\n                    <jats:italic>MYH7<\/jats:italic>\n                    and faster maturation of myotubes. LG-MEM also altered LC3B expression patterns, while transmission electron microscopy showed fewer excess autophagosomes and autolysosomes along with more prominent myofibril-like ultrastructure, consistent with more efficient autophagic activity and organelle remodeling. These findings suggest that a physiological metabolic environment facilitates autophagy-linked organelle remodeling in hEUS myoblasts and that 3HB acts as a fine-tuning signal, potentially supporting metabolism-oriented approaches for stress urinary incontinence.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43453-4","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:26:03Z","timestamp":1773671163000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiological medium and 3-hydroxybutyrate modulate autophagy-linked organelle remodeling in human external urethral sphincter myoblasts"],"prefix":"10.1038","volume":"16","author":[{"given":"Hironori","family":"Kai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinro","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Hamamatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Shiraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"issue":"4","key":"43453_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1097\/SPV.0000000000001127","volume":"28","author":"UJ Patel","year":"2022","unstructured":"Patel, U. 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