Determinants of intra-individual variation in adaptability to resistance training of different volumes

Systematic resistance training positively affects skeletal muscle mass and functional characteristics of the neuro-muscular system. By varying exercise variables such as training volume, the training can be individualized. On what indications such variations should be performed are not clear since individuals vary with regards to volume-dependence in training outcomes such as muscle mass and strength. The primary aim of this thesis was to relate the adaptive response of low and moderate volume resistance training to individual characteristics in untrained individuals. Secondary aims were to characterize exercise-volume dependence in muscle characteristics and determine a time course profile of ribosomal biogenesis-markers in response to resistance training. In Study I (Paper I), young, healthy, and previously untrained male and female participants (n = 34) trained for 12 weeks (2-3 sessions x week-1) with low (a single set per exercise) or moderate volume (three sets per exercise) allocated to either leg in a contralateral fashion. Muscle cross-sectional area and strength measurements were made before and after the intervention. Biopsy sampling from m. vastus lateralis was performed before and after the intervention and before and one hour after the fifth session. Training-induced muscle hypertrophy and strength gains were shown to be volume dependentas both variables increased to a greater extent in response to moderate-volume training. These effects coincided with greater activation of mTORC1 signaling, higher abundance of markers related to ribosomal biogenesis, and greater reduction in fiber-type IIX proportions. Thirteen and sixteen participants, respectively, were identified as having additional benefits of moderate- over low-volume training on muscle hypertrophy and strength. The additional benefit of moderate-volume training for muscle hypertrophy and strength gains was associated with greater accumulation of total RNA at Week 2 in the moderate-volume leg, indicating that the ability to differentiate ribosomal biogenesis in the initial phase predicted long-term benefits of moderate over low training volume. Based on RNA quality, a subset (n = 25) of participants originally included in Study I was used in a follow-up analysis of transcriptome characteristics (Paper II). Accumulation of RNA due to increased ribosomal biogenesis in response to resistance training led to different amounts of tissue being used in analyses as a fixed amount of total RNA was used in sample preparation. When this was accounted for through normalization strategies, dose-dependent increased expression of genes primarily related to the extracellular matrix was identified after two weeks of training in rested-state muscle. In contrast, after the intervention, no dose-dependencies were observed. When not accounting for the amount of tissue used, results indicated counter intuitive increased expression of genes in the low-volume condition. Given the apparent importance of ribosomal biogenesis identified in Study I, Study II (Paper III) aimed to describe a time course of accumulation of markers of ribosomal abundance in response to resistance training. Furthermore, it was hypothesized that fluctuations in training volume and training cessation would be reflected in markers of ribosomal biogenesis. Eighteen participants were allocated to either a training group (n = 11) or a control group (n = 7). The training group performed unilateral knee extension with constant (6 sets) or variable volume (6, 3, and 9 sets in sessions 1-4, 5-8, and 9-12, respectively). Muscle biopsies were sampled from m vastus lateralis in the training group before and 48 hours after the first session and 48 hours after sessions 4, 5, 8, 9, 12, and after eight days of de-training. Biopsies were also sampled in the control group at baseline, after 48 hours, and after 2-4 weeks. Twelve resistance-training sessions led to muscle growth and gains in strength in the training group compared to the control group. Training also led to increases in total RNA, ribosomal RNA, increased protein levels of upstream binding factor (UBF), and ribosomal protein S6 (rpS6). Total RNA increased in a curve-linear fashion, most rapidly in response to the first four sessions, followed by a plateau and peak values of ∼50% above baseline values after eight sessions. Variations in training volume did not affect the observed increase in either total RNA or any ribosomal RNA. UBF protein levels were related to total RNA levels after controlling for time. Increases in total RNA levels, in turn, predicted training-induced muscle hypertrophy. After eight days of no training, total RNA and specific ribosomal RNA species decreased without muscle mass changes, indicating reduced concentrations and biosynthesis of ribosomes in response to de-training. These results underline a determinant role for ribosomal biogenesis in resistance training-induced muscle hypertrophy and that ribosomal biogenesis is sensitive to training cessation. Overall, this thesis demonstrates a determining role of ribosomal biogenesis in adaptations to resistance training. In addition, it broadly characterizes the effect of training volume on multiple aspects of skeletal muscle biology