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

In light of the current global prevalence of overweight and obesity, the associated health risks, and the continuing adoption of sedentary lifestyle, this thesis investigated some of the factors that contribute to exercise adherence, directly comparing high-intensity whole body interval training and continuous endurance training. 68 inactive university aged adults (Age: 21.4±3.4 yrs, BMI: 25.6±4.6 kg/m2, VO2peak 40.1±5.7 ml/kg/min) were randomized into one of three groups; a non-exercise control, whole body high intensity training, or continuous endurance training. Aerobic capacity measurements, time to completion trials, muscular endurance, and core strength measures were taken at pre, post and follow up testing sessions. Psychological questionnaires were also administered during exercise as well as throughout the study. Following the intervention both exercise groups demonstrated equivalent improvements in aerobic performance, with only the interval group experiencing improved muscular and core endurance. After the 2-month follow up testing sessions the interval group lost all aerobic and core adaptation, with endurance only experiencing a partial loss. This finding indicates that the interval group did not adhere to exercise at a level that was high enough to preserve the adaptations associated with training. This finding is further supported by the psychological factors measured throughout this study, including acute affect, enjoyment and intentions to engage in future exercise. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2013-10-31 15:08:15.524

High-density lipoprotein (HDL) with its cardio- protective effects has provided remarkable optimism to the ever-increasing incidences of coronary artery disease. Therefore, the aim of this randomized, comparative, research trial was to determine whether endurance exercise training, weight training and/or a combination of aerobic and weight training can be utilized in the management of high-density lipoprotein cholesterol (HDL-C). Subsequent to the 16-week intervention period, dependant t-Tests revealed that the non-exercising and weight training groups demonstrated non- significant mean 1.3% (p = 0.754) and 11.1% (p = 0.069) increases in fasting serum HDL-C, respectively. Conversely, there was a significant increase in HDL-C following the 16 weeks of endurance training (p = 0.003) and combination training (p = 0.005) (22.4% and 37.9%, respectively). Further, Spearman’s rho indicated no correlations between HDL-C and BMI (r = -0.131), percentage body fat (r = - 0.141), cholesterol intake (r = - 0.026) and total fat intake (r = - 0.239). The absence of changes in these inter-correlations indicated that changes in these parameters had no effect on the HDL-C. On the contrary, moderate correlations were established between HDL-C and number of cigarettes smoked daily (r = - 0.344) and intake of saturated fat (r = - 0.317) indicating that exercise effect on these variables could have indirectly contributed significantly in altering HDL- C in the endurance and combination training groups. As such, endurance and combination training can be utilized as an effective method in the management of HDL-C in sedentary male smokers.

The effects of either 12-wk of high-intensity endurance or resistance training on resting metabolic rate (RMR) were investigated in 47 males aged 18-35 y. Subjects were randomly assigned to either a control (C), resistance- trained (RT) or endurance-trained (ET) group. After training both exercise groups showed significant declines in relative body fat either by reducing their total fat weight and maintaining fat-free weight (ET) or by reducing their total fat weight and increasing fat-free weight (RT). RMR did not significantly change after either training regimen although a small decline in energy intake was observed along with an increase in energy expenditure [ET, 2.721 MJ (650 kcal) per training day]. These results suggest that both endurance and resistance training may help to prevent an attenuation in RMR normally observed during extended periods of negative energy balance (energy intake < expenditure) by either preserving or increasing a person's fat-free weight.

Les buts de cette thèse étaient d’explorer les effets de la composition corporelle, de la surcharge pondérale et d’un programme d'entraînement pluridisciplinaire en endurance sur le contenu minéral osseux (CMO) et la densité minérale osseuse (DMO) chez les adolescents. Au total 4 études ont été menées. La première étude avait comme but d’explorer la contribution relative de la masse maigre et de la masse grasse aux valeurs de DMO chez 35 filles et 65 garçons français. Celle-ci a montré que la masse grasse est un déterminant positif de la DMO chez les filles mais pas chez les garçons. En effet, la masse maigre était le meilleur déterminant de la DMO chez les garçons. La deuxième et la troisième étude avaient comme objectif d’étudier les effets de la surcharge pondérale sur le CMO et la DMO du corps entier, du rachis lombaire et de la hanche chez des adolescentes libanaises. Ces 2 études ont montré que la surcharge pondérale est accompagnée d’une augmentation des valeurs absolues de CMO et de DMO. Cependant, après ajustement par le poids, ces différences disparaissent. Dès lors, ces études suggèrent que la DMO des filles en surcharge pondérale soit bien adaptée à l’excès de poids. La quatrième étude a étudié les effets de 12 semaines d’entraînement en endurance sur le CMO et la DMO chez des adolescentes obèses, en surpoids et normo-pondérées. Cette étude a montré une augmentation des valeurs de DMO dans les 3 groupes alors que le CMO n’a augmenté que dans le groupe obèse. Cette étude confirme le rôle positif de l’exercice physique sur la DMO chez les adolescentes obèses et non obèses. / The aims of this thesis were to explore the effects of body composition, overweight and of an endurance training program on bone mineral content (BMC) and bone mineral density (BMD) in adolescents. 4 studies were undertaken to achieve this goal. The first study explored the relative importance of lean and fat mass on BMD in a group of adolescent girls and boys. This study showed that fat mass is a positive determinant of BMD in girls but not in boys. In fact, lean mass was the best positive determinant of BMD in boys. The studies 2 and 3 aimed at studying the effects of overweight on whole-body, lumbar spine and hip BMD in Lebanese adolescent girls. These studies showed that the crude values of BMC and BMD were higher in overweight girls compared to controls. However, there were no differences in BMC or BMD between the two groups after adjusting for weight. Therefore, these studies suggest that the BMD of the overweight girls adapts to the increased body weight. The last study explored the effects of 12 weeks of endurance training on BMC and BMD in obese, overweight and normal-weighted sedentary adolescent girls. The BMD increased in the three groups. However, the whole-body BMC increased only in the obese group. This study confirmed the positive effects of physical exercise on BMD in obese and non-obese adolescent girls.

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<p> In order to investigate possible negative effects of endurance training on muscle strength and power, 10 healthy young men underwent 10 weeks of endurance training. Subjects trained unilaterally on a cycle ergometer so that their opposite leg served as a control. Training consisted of 30 min per day for 3 days per week and progressed to 60 min per day for 5 days per week by the seventh week of training. This volume of endurance training exceeds the upper limits of that normally performed by athletes who compete in power sports. The exercise intensity was initially ~75% of pre-training maximum power output and was increased over time to maintain a training heart rate of 140-160 beats per minute. Endurance, strength, and power variables were assessed in each leg before and after the training period. Measurements included electrically stimulated twitch characteristics of the quadriceps, single-leg V̇O2peak and lactate threshold (Tlac), single-leg take-off vertical jump power indices from a force platform, and maximal leg press strength at a low-(60°/s) and high-velocity (300°/s). Needle biopsies were taken from the quadriceps femoris before and after the training period, and analyzed for fibre-type proportions, fibre area, oxidative enzyme activity and capillary density. Post-training, subjects increased leg V̇O2peak (7%) and Tlac in the trained leg. Leg press strength was unaffected by training. Vertical jump power was not impaired nor were evoked twitches. Following training, there was a decrease in % type IIb and an increase in % type IIa fibres (p<0.05). There were no significant changes in fibre area. Percent fibre area increased for type I and IIa and decreased for type IIb fibres in the trained leg (p<0.05). These data indicate that a 10-week endurance-training program increases aerobic power but does not impair muscle strength or power.</p> / Thesis / Master of Science (MSc)

Insulin resistance (IR), T2DM, and obesity together form a cluster of interrelated metabolic challenges that may be linked by metabolic inflexibility. Metabolic inflexibility is characterized by the resistance to switching substrate oxidation preference based on substrate availability and can be measured in either fasted or insulin-stimulated conditions. As the largest site for glucose disposal and a primary tissue influencing regulation of blood glucose concentrations, skeletal muscle likely plays a central role in regulating substrate oxidation preference based on substrate availability. Skeletal muscle lipotoxicity caused by an impaired regulation of fat uptake and oxidation is postulated to disrupt insulin signaling and lead to skeletal muscle IR. High dietary saturated fat intake results in reduced basal fat oxidation and a resistance to switching to carbohydrate oxidation during insulin-stimulated conditions in susceptible individuals. This metabolic inflexibility may lead to an accumulation of intramyocellular species that impair insulin signaling. Endurance exercise training improves the capacity for fat oxidation in metabolically inflexible individuals. However, relatively little is known about how endurance exercise training influences substrate oxidation preference when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on substrate metabolism in skeletal muscle of sedentary and endurance trained (ET) males. Healthy, sedentary (n=17) and ET (n=7) males first consumed a 10-day moderate carbohydrate diet (55% carbohydrate, 30% total fat, <10% saturated fat) isocaloric to their individual energy requirements and then underwent a 4- hour high fat challenge testing session. During the session, they consumed a high fat meal (820 kcals; 25% carbohydrate, 63% total fat [26% saturated fat]), and skeletal muscle biopsies were taken in the fasted and 4-hour postprandial conditions. Participants then consumed a 5-day HFD (30% carbohydrate, 55% total fat, 25% saturated fat) and repeated the high fat challenge testing session. Substrate oxidation measures were performed on the collected skeletal muscle tissue, and the meal effect, defined as the percent change from the fasting to 4- hour postprandial condition, for each measure was calculated. There was a HFD by physical activity group interaction on meal effect for metabolic flexibility (P<0.05) and a HFD effect on meal effect for glucose oxidation (P<0.05). Meal effects for metabolic flexibility and glucose oxidation were maintained in the ET (20 ± 4% to 41 ± 21% and 128 ± 92% and 41 ± 15%, respectively; both P>0.05) but decreased in the sedentary (34 ± 7% to 4 ± 5% and 78 ± 26% to -21 ± 6%, respectively; both P<0.01) group. There were trends toward HFD effects on reductions in meal effects for total (P=0.062) and incomplete (P=0.075) fat oxidation, which were driven primarily by an increase in fasting total (12.1 ± 2.6 nmol/mg protein/h to 18.5 ± 2.3 nmol/mg protein/h; P<0.01) and incomplete (11.5 ± 2.5 nmol/mg protein/h to 17.6 ± 2.3 nmol/mg protein/h; P<0.01) fat oxidation in the ET group as a result of the HFD. Fasting total and incomplete fat oxidation did not change in the sedentary group (7.3 ± 0.8 nmol/mg protein/h to 7.8 ± 0.8 nmol/mg protein/h and 6.8 ± 0.7 nmol/mg protein/h to 7.2 ± 0.8 nmol/mg protein/h, respectively; both P>0.05). Overall, these findings suggest the ET state attenuates deleterious effects of a short-term HFD on reduced metabolic flexibility and insulin-stimulated glucose oxidation. In addition, a HFD-induced reduction in fat oxidation during the fasted-to-fed transition may be caused by differing mechanisms in sedentary and ET individuals. These findings provide a basis for future work targeting the elucidation of potential mechanistic differences in substrate oxidation preference between sedentary and ET individuals. / Ph. D. / Type 2 diabetes (T2DM) is a commonly occurring disease worldwide, and treatment of the disease is considerably burdensome for individuals and societies. T2DM is closely related to insulin resistance (IR) and obesity, and in each of these conditions, the characteristic of metabolic inflexibility has been observed. Metabolic inflexibility is a reduced ability to adjust fat or carbohydrate utilization for energy based on the availability of each of these macronutrients. Skeletal muscle may be an important tissue in the regulation of macronutrient utilization since it plays a key role in blood glucose regulation. High dietary saturated fat intake may lead to metabolic inflexibility in skeletal muscle in susceptible individuals. This metabolic inflexibility may result in increased storage of fat within skeletal muscle, which is hypothesized to disrupt insulin signaling. This disruption can lead to IR. Endurance exercise training improves metabolic flexibility. However, little is known about how endurance exercise training influences macronutrient utilization when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on macronutrient utilization in skeletal muscle of sedentary and endurance trained (ET) males. Seventeen healthy, sedentary males and seven ET males first consumed a 10-day moderate-carbohydrate diet that was provided by the study investigators and designed to keep each participant weight stable. Participants then underwent a high fat challenge testing session in which they consumed a high fat meal and had skeletal muscle biopsies taken both before and after the meal. Participants then consumed a 5-day HFD, also designed to keep them weight stable, and repeated the high fat challenge testing session. Macronutrient utilization measures were performed on the collected skeletal muscle samples. Overall, metabolic flexibility was reduced in the sedentary group but was maintained in the ET group, which suggests that ET individuals may be protected against developing a HFD-induced metabolic inflexibility in skeletal muscle and its associated downstream negative effects on insulin signaling. In addition, fat utilization during the high fat challenge meal decreased in both sedentary and ET individuals as a result of the HFD. However, fat utilization in the fasted state was higher in ET individuals after the HFD compared with baseline, but fat utilization was the same in sedentary individuals before and after the HFD. This suggests there may be differences between sedentary and ET individuals in the mechanisms involved in the adjustment of fat utilization to dietary fat intake. Further research is needed to understand these differences, as they may play important roles in understanding how IR and T2DM develop.