ArticleJournal of cachexia, sarcopenia and muscle2026
Exploring the Impact of Urolithins A and B on Muscle Health: A Transcriptomic Analysis in Human Myotubes.
Article in Journal of cachexia, sarcopenia and muscle, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundUrolithin A (UA) and urolithin B (UB) are gut microbiota-derived metabolites of ellagitannins reported to influence mitochondrial function, inflammation and muscle metabolism. Their comparative transcriptomic effects in human skeletal muscle cells remain undefined. We characterized UA- and UB-induced molecular responses in primary human myotubes.
methodsPrimary CD56
resultsUA and UB significantly modulated 1918 and 339 genes, respectively (FDR < 0.01; |log2FoldChange| > 0.32), demonstrating distinct transcriptomic reprogramming in human myotubes. Pathway analysis showed that UA predominantly affected oxidative phosphorylation, mitochondrial dysfunction, inositol phosphate metabolism and glycosylation pathways (N-linked glycosylation z score 2.11), whereas UB activated cholesterol biosynthesis (z score 2.45), mevalonate pathway (z score 2.00), adipogenesis (z score 1.41) and inhibited eicosanoid signalling (z score -2.71). At 5 μM (RNA-seq), UA increased NOTCH1 (+73%), MYMX (+70%), PANX1 (+50%) and MSTN (+64%), and decreased FGF9 (-75%), ICAM5 (-52%) and MRLN (-33%), whereas UB decreased IGFN1 (-75%), TGFBI (-60%) and STC2 (-35%) and increased TGM2 (+59%). UA increased LIF (+80%) and decreased PTGS1 (-41%) and IL17B (-49%), whereas UB decreased PTGS1 (-43%) and increased IL17B (+45%). RT-qPCR validation confirmed UA-induced increases in NOTCH1 (5 μM, p = 0.0471), MYMX (10 μM, p = 0.0363), and PANX1 (5 μM, p = 0.0012; 10 μM, p = 0.0065), dose-dependent reductions in FGF9 (r
conclusionsUA and UB induce quantitatively and qualitatively distinct transcriptomic programmes in human myotubes. UA preferentially modulates mitochondrial and inflammatory pathways, whereas UB primarily affects lipid metabolism and muscle-related processes. These findings provide mechanistic insight into urolithin-mediated regulation of human muscle cell biology able Stro.
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