Interaction of nutrient availability and endurance training on skeletal muscle adaptation in trained humans

Nutrient availability and exercise training are two potent modulators of skeletal muscle adaptation. While the effects of nutrient provision or training alone on muscle adaptation have been well researched, the interactive effects of these two stressors on whole-body metabolism and skeletal muscle adaptation are less well understood, especially in well-trained individuals. Furthermore, until recently, little work has been undertaken to determine some of the mechanisms that underlie the changes in muscle metabolism that result from the interaction of nutrient and contractile status. Accordingly, the primary aims of the experiments undertaken for this thesis were: 1) to enhance our understanding of how skeletal muscle nutrient availability interacts with exercise training to promote changes in muscle and whole-body metabolism in well-trained athletes, and 2) to determine potential mechanisms that might underlie some of these adaptations. The first experiment was undertaken to determine the effects of a dietary periodisation strategy termed "fat adaptation and CHO restoration" on subsequent changes in skeletal muscle fuel storage profile, whole-body metabolism and the potential mechanisms underlying these changes in well-trained humans. Compared with HCHO, FAT-adapt increased resting muscle TG stores and resting AMPK-α1 and -α2 activity but attenuated the exercise-induced rise in AMPK-α1 and AMPK-α2 activity. These results demonstrate that AMPK-α1 and AMPK-α2 activity and fuel selection in skeletal muscle in response to exercise can be manipulated by diet and/or the interactive effects of diet and exercise training. The second experiment was undertaken to determine the effects of a cycle training programme (3-wk) in which selected training sessions were commenced with low muscle glycogen content on training capacity, muscle adaptation, whole-body metabolism and subsequent endurance performance. Compared with training daily, training twice every second day compromised high-intensity training capacity. While selected muscle markers of training adaptation were enhanced with twice-a-day training, performance improvement was similar after once daily or twice every second day training programmes. In the subsequent study, it was showed that the enhanced adaptations seen in the previous study were likely to be mediated by AMPK and/or other unidentified downstream targets. In summary, the results of the studies undertaken for this thesis provide novel insights into the mechanisms by which the manipulation of nutrient availability and subsequent muscle fuel storage profile interact with endurance exercise training to promote changes in skeletal muscle metabolism and adaptation in well-trained athletes. Specifically, fat adaptation and CHO restoration increased resting muscle TG and the subsequent metabolic responses were shown to be mediated by the AMPK-ACC signalling axis. In addition, selected markers of training adaptation were enhanced when well-trained subjects undertook a chronic (3-wk) intervention in which they commenced selected sessions with reduced compared to muscle glycogen content with AMPK again implicated as the mediator of the adaptations observed. It was concluded that the changes in AMPK activation observed in these studies could be due to altered fuel status (i.e., increased muscle lipid availability, reduced muscle glycogen content), a greater adaptive resp onse when training with low muscle glycogen availability, or most likely, the interactive effects of both these factors