Molecular bases of training adaptation

Coffey, V 2006, Molecular bases of training adaptation, Doctor of Philosophy (PhD), Medical Sciences, RMIT University.

Document type: Thesis
Collection: Theses

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Title Molecular bases of training adaptation
Author(s) Coffey, V
Year 2006
Abstract The molecular events that promote or inhibit specific training adaptations (i.e. skeletal muscle hypertrophy or mitochondrial biogenesis) are not completely understood. Accordingly, there is a need to better define both the acute and chronic responses to divergent exercise stimuli in order to elucidate the specific molecular mechanisms that ultimately determine skeletal muscle phenotype. Therefore, the primary aims of the studies undertaken for this thesis were to examine the acute molecular adaptation responses in skeletal muscle following resistance and endurance training.

In order to determine the acute molecular events following repeated bouts of exercise, the study described in Chapter Two compared a high-frequency stacked training regimen designed to generate a summation of transient exercise-induced signalling responses with a conventional-frequency resistance training protocol. Groups (n= 6) of Sprague-Dawley rats performed either high-frequency training (four exercise bouts consisting of 3 - 10 repetitions separated by 3 h) or conventional-frequency training (three exercise bouts consisting of 4 - 10 repetitions with 48 h between sessions). Protocols were matched for total work, and repetitions were performed at 75% one-repetition maximum with 3 min recovery between sets. White quadriceps muscle was extracted 3 h after every training bout, and 24 and 48 h following the final exercise session of each protocol. AKT phosphorylation was significantly decreased 3 h following the 2nd bout of high-frequency training, an effect that persisted until 48 h after the final exercise bout (P less than 0.05), while the phosphorylation state of this kinase was unchanged with conventional training. These results suggest that high-frequency training suppressed IGF-1 mediated signalling. Furthermore, high-frequency training generated sustained and coordinated increases in TNFá and IKK phosphorylation (P less than 0.05), indicating an extended response of inflammatory signalling pathways. Conversely, and irrespective of an initial increase after the first bout of exercise, TNFá signalling ultimately returned to control Abstract values by DAY 5 of conventional-frequency training, indicative of a rapid adaptation to the exercise stimulus. Notably, despite differential AKT activation there were similar increases in p70 S6K phosphorylation with both training protocols. These results indicate high-frequency resistance training extends the transient activation of inflammatory cytokine-mediated signalling and results in a persistent suppression of AKT phosphorylation, but these events do not appear to inhibit kinase activity proximal to translation initiation.

The aim of the study described in Chapter Three was to determine the effect of prior training history on selected signalling responses after an acute bout of resistance and endurance exercise. Following 24 h diet / exercise control 13 male subjects (7 strength-trained and 6 endurance-trained) performed a random order of either resistance (8 x 5 maximal leg extensions) or endurance exercise (1 h cycling at 70% peak O2 uptake). Muscle biopsies were taken from the vastus lateralis at rest, immediately and 3 h post-exercise. AMPK phosphorylation increased after cycling in strength-trained, but not endurance-trained subjects (P less than 0.05). Conversely, AMPK was elevated following resistance exercise in endurance-, but not strength-trained subjects (P less than 0.05). Thus, AMPK was elevated only when subjects undertook a bout of exercise in a mode of training to which they were unaccustomed. Surprisingly, there was no change in AKT phosphorylation following resistance exercise regardless of the training background of the subjects. In the absence of increased AKT phosphorylation, resistance exercise induced an increase in p70 S6K and ribosomal S6 protein phosphorylation in endurance-trained but not strength-trained subjects (Pless than 0.05). AKT phosphorylation was increased in endurance-trained, but not strength-trained subjects after cycling (P less than 0.05). These results show that a degree of signalling "response plasticity" capable of diverse adaptive compliance is conserved at opposite ends of the adaptation continuum. Furthermore, the adaptive phenotype associated with a prolonged training history alters the subsequent signalling responses with divergent exercise stimuli.

The third study described in Chapter Four quantified the acute sub-cellular mRNA responses in muscle to habitual and unfamiliar exercise modes. This study employed the same subjects and protocols outlined in Chapter Three and analysis was performed on muscle biopsies taken at rest and 3 h after an exercise bout. Gene expression was analysed using Real-Time PCR with changes normalised relative to pre-exercise values. Following cycling exercise peroxisome proliferator activated receptor gamma co-activator-1 alpha, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA abundance was significantly increased in both endurance and strength-trained subjects (P less than 0.05). This finding indicates that the adaptive phenotype of these athletes did not produce a disparity in the mRNA response of these 'metabolic genes'. Similarly, muscle atrophy F box protein (MAFBx) mRNA increased in both groups (P less than 0.05) suggesting that a prolonged endurance training stimulus may increase the activity of pathways involved in the regulation of muscle atrophy. Unexpectedly, MyoD and Myogenin mRNA increased in endurance-trained subjects after cycling. Accordingly, it seems plausible to suggest that these regulators of satellite cell activity may have additional roles in skeletal muscle metabolism. Finally, high-intensity resistance exercise did not induce any change in mRNA abundance of selected 'myogenic' genes in either group of subjects, despite a decrease in MAFBx and Myostatin mRNA in endurance-trained subjects. It may be that in highly-trained athletes a greater volume or repeated bout effect is required to initiate anabolic gene expression. Taken collectively, these results indicate that prior training history can modify the acute mRNA changes in skeletal muscle in response to exercise. Indeed, the data indicate that independent of exercise mode, the gene responses in skeletal muscle from endurance-trained athletes are more sensitive to alterations in the cellular milieu than strength-trained subjects.

In summary, the work from the studies undertaken for this thesis provides novel information regarding the effects of the frequency of the training stimulus on signalling responses in skeletal muscle. Specifically, high-frequency resistance training does not enhance anabolic signal transduction and may exacerbate inflammation and atrophy. In regard to the effects of prior contractile history on early signalling and mRNA responses, divergent exercise induces a mode specific molecular response that is altered by the training-induced phenotype of the muscle, highlighting the need for extensive training overload in highly trained athletes.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Medical Sciences
Keyword(s) Adaptation (Physiology)
Sports -- Physiological aspects
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