While molecular signal transduction pathways are well described, less is known about selective protein degradation pathways and changes of the human skeletal muscle metabolome in response to resistance exercise (RE). We determined that maximal eccentric RE leads to a significant degree of z-disc streaming and myofibrillar damage associated with a significant degree of unfolding and degradation of filaminC (FlnC) proteins. FlnC proteins act by crosslinking actin filaments in the sarcomeric z-disc and further as molecular sensors of damage. Its degradation is coordinated via chaperone-assisted selective autophagy (CASA) by the cochaperone BAG3 which also controls increased FlnC expression. › In contrast to low intense RE, maximal eccentric RE induces a significant reduction of FlnC and BAG3 within 24 h after acute RE. In a chronic RE intervention (13 RE units; 3 times per week) a progressive but not constant training intensity was associated with a significant increase in FlnC levels over five weeks of RE. This was accompanied by a fast reduction of z-disc streaming and myofibrillar damage and attributes CASA-mediated FlnC incorporation into z-discs a potential role in mediating the “Repeated bout” effect. As it can be assumed that during frequent RE and in a growing muscle various metabolic pathways will be activated, we hypothesized that branches of the skeletal muscle metabolome will change acutely and also after several weeks of RE. › In a combined approach using liquid chromatography followed by detection through mass spectrometry we detected 589 metabolites within biopsy samples in which we also found a significant increase in type I and II myofiber diameter. Metabolites of the amino acid and nucleotide metabolism increased significantly after the first unaccustomed RE session while being reduced up to the 13th RE session. In contrast, metabolites of the lipid metabolism were significantly reduced up to the last training session indicating a reduction in skeletal muscle lipid content induced by RE. › We conclude that RE exerts the acute and chronic adaptation of the metabolomic signature and structural integrity of skeletal muscle which is substantially influenced by the magnitude of loading.     «

While molecular signal transduction pathways are well described, less is known about selective protein degradation pathways and changes of the human skeletal muscle metabolome in response to resistance exercise (RE). We determined that maximal eccentric RE leads to a significant degree of z-disc streaming and myofibrillar damage associated with a significant degree of unfolding and degradation of filaminC (FlnC) proteins. FlnC proteins act by crosslinking actin filaments in the sarcomeric z-disc...     »