title: The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts.
abstract: Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maléne E
authors.initials: ME
authors.lastname: Lindholm
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), Solna, Sweden.
authors.forename: Stefania
authors.initials: S
authors.lastname: Giacomello
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), Solna, Sweden.
authors.forename: Beata
authors.initials: B
authors.lastname: Werne Solnestam
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.|Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helene
authors.identifier: http://orcid.org/0000-0002-5583-2088
authors.initials: H
authors.lastname: Fischer
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), Solna, Sweden.
authors.forename: Mikael
authors.identifier: http://orcid.org/0000-0003-0839-2451
authors.initials: M
authors.lastname: Huss
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), Solna, Sweden.
authors.forename: Sanela
authors.initials: S
authors.lastname: Kjellqvist
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Johan
authors.identifier: http://orcid.org/0000-0002-7000-466X
authors.initials: CJ
authors.lastname: Sundberg