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Our aim was to identify disease\u2010related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6\u2010month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergstr\u00f6m needle biopsy) before and after training from patients and sedentary age\/sex\/body mass index\u2010matched controls. [<jats:sup>14<\/jats:sup>C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3\u00a0days) and acute (3\u00a0h) metabolic challenge (the saturated fatty acid palmitate, 100\u00a0\u03bc<jats:sc>m<\/jats:sc>). Reduced oxidative (intermediate metabolites, \u221249%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.034) and non\u2010oxidative (diglycerides, \u221238%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013) lipid metabolism was identified in palmitate\u2010treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V\/ATP synthase (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.012\/0.005) and adipose triglyceride lipase in patients compared to controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.045) (immunoblotting). Importantly, 6\u00a0months of training in IIM patients improved lipid metabolism (CO<jats:sub>2<\/jats:sub>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.010; intermediate metabolites, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.041) and activation of AMP kinase (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.007), and nearly normalized palmitate\u2010induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients\u2019 clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non\u2010immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6\u2010month training intervention mitigated disease effects in muscle cells <jats:italic>in vitro<\/jats:italic>, indicating the existence of epigenetic regulatory mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280468","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T12:09:44Z","timestamp":1602850184000},"page":"207-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6\u00a0months of training"],"prefix":"10.1113","volume":"599","author":[{"given":"M.","family":"Nemec","sequence":"first","affiliation":[{"name":"Biomedical Research Centre Slovak Academy of Sciences Institute of Experimental Endocrinology  Bratislava 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