ArticleAnnals of the rheumatic diseases2025
Mitochondria-centred metabolomic map of inclusion body myositis: sex-specific alterations in central carbon metabolism.
Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Multilevel impairment of mitochondrial respiration with sex-specific signatures in inclusion body myositis.bioRxiv : the preprint server for biology · 2026Article
- Energy metabolism dysregulation in idiopathic inflammatory myopathies: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
objectivesTo benchmark metabolomic signatures of inclusion body myositis (IBM) in muscle tissue, highlighting sex-specific differences and the correlation with clinical parameters.
methodsA total of 37 IBM patients and 22 controls without myopathy were included. All participants had bulk RNA sequencing performed previously. Clinical parameters included disease duration and manual muscle test (MMT) scores. Discovery metabolite screening and quantitative targeted metabolomics platforms were used. Levels of metabolites and RNA-metabolomic integrated modules were correlated with clinical parameters and the mitophagy marker, p-S65-Ubiquitin (p-S65-Ub).
resultsIBM muscle samples showed elevated citric acid (TCA) cycle intermediates and anaplerotic amino acids. Proximal glycolytic intermediates were decreased, while pentose phosphate pathway (PPP) metabolites were increased. Short-chain acylcarnitines were lower in IBM males but not in females. Lastly, nucleic acid bases were increased, and nucleotides were decreased. MMT correlated with PPP metabolites and nucleic acid bases, and inversely correlated with glycolysis metabolites and mono/diphosphate nucleotides. MMT also correlated with several amino acids, including cysteine, taurine, carnosine, and sarcosine. Acylcarnitines correlated with disease duration only in males. Four RNA-metabolomic integrated modules demonstrated significant correlations. The strongest correlations were observed between the pink module and both sexes and p-S65-Ub. MMT and p-S65-Ub correlated with 3 and 2 modules, respectively. The enriched pathways were related to central carbon metabolism, cytokine/chemokine signalling, neurotransmission, and mitogen-activated protein kinase (MAPK)/RAS signalling. Males had relatively similar correlations to the combined-sex analysis, while females had no significant correlation with any module.
conclusionsIBM is associated with clinically significant alterations in central carbon metabolism, with the strongest RNA-metabolomic-clinical correlations observed in males. Further research is needed to explore the role of these metabolic changes in IBM pathogenesis and their progression over time.
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