نبذة مختصرة : Although there is growing evidence that both physical activity and physical fitness are important during adulthood in attenuating the risk factors for cardiometabolic disease, and in enhancing cognitive function, there is limited information on their effects during adolescence which are important years of growth. Therefore, this thesis examines the importance of physical activity and physical fitness for both cardiometabolic health and cognition during these vital adolescent years. Throughout the thesis, blood glucose and plasma insulin concentrations were measured in the fasted state to calculate the homeostatic model assessment of insulin resistance (HOMA-IR), as well as in the 3 h postprandial window following a standardised, ecologically valid, meal. Furthermore, in Chapters IV and VIII a range of pro- and anti-inflammatory cytokines (IL-6, IL-10, IL-15 and IL-1β) were also measured as an indication of low-grade chronic inflammation. These measures formed the central focus of the risk factors for cardiometabolic disease. The battery of cognitive function tests used in the present thesis was administered via laptop computers. The Stroop test (Chapters IV, VII and VIII; assessing executive function), Sternberg paradigm (Chapters IV, VII and VIII; assessing working memory), the Flanker test (Chapter IV and VIII; assessing executive function) and the visual search test (Chapter IV; assessing visual perception) were used to provide a holistic view of cognitive function. Additionally, brain-derived neurotrophic factor (BDNF) was also measured in Chapters IV, VII and VIII. The first experimental chapter (Chapter IV) examined the cross-sectional associations between physical fitness (measured by distance covered on the multi-stage fitness test), device measured physical activity and adiposity, and risk factors for cardiometabolic disease and cognitive function in 113 adolescents (63 girls). These associations were examined in the group overall, as well as separately for year 7 (11-12 years, n = 70, 35 girls) and year 10 (14-15 years, n = 43, 27 girls) participants. The main findings of chapter IV were that adolescents with a higher physical fitness had faster response times for several cognitive domains (working memory, executive function, and visual perception), and a higher IL-15 concentration. When considering novel physical activity metrics from accelerometery derived data, greater volume (β = -0.55 mmHg, p = 0.005) and more high-intensity activity (β = 10.92 mmHg, p = 0.006) were associated with lower mean arterial blood pressure; with a stronger association in year 10 participants. Waist circumference was positively associated with systolic blood pressure in the sample overall (β = 0.32 mmHg, p = 0.038), and positively associated with IL-6 concentration in the year 10 participants only (β = 0.03%, p = 0.026). Furthermore, when considering the differences between year group and sex, the key findings were that year 7 girls had higher concentrations of pro-inflammatory cytokine IL- 6 (2.59 ± 1.33 pg·ml-1), when compared to boys of the same age (1.70 ± 1.06 pg·ml-1, p < 0.001) and when compared to year 10 girls (1.17 ± 0.55 pg·ml-1, p < 0.001). This study highlights the importance of physical activity, physical fitness and adiposity, for both cardiometabolic health and cognition during adolescence. It also draws attention to the less favourable cardiometabolic health profile in year 7 girls. The second experimental chapter (Chapter V) examined the determinants of the postprandial glycaemic and insulinaemic response to a standardised meal in a large sample of adolescents (n = 108; 11-13 years). The main findings were that both adiposity (particularly central adiposity, as measured by waist circumference) and physical fitness (measured as distance covered on the MSFT) were important determinants of the postprandial insulinaemic response. Specifically, waist circumference (β = 0.41, p < 0.001) and HOMA-IR (β = 0.37, p < 0.001) were positively associated, and distance run on the MSFT negatively associated (β = -0.16, p = 0.031), with the postprandial insulinaemic response; and collectively they explained 51% of the variance. There was no association between the predictors used and the glycaemic postprandial response (R2 = 0.03, p = 0.198). This study shows that high physical fitness attenuates, and adiposity exacerbates, the postprandial insulinaemic response to a standardised meal. In addition, physical fitness was an independent determinant (even when adiposity was accounted for) of the postprandial insulinaemic responses. The third experimental chapter (Chapter VI) examined the effect of football activity and physical fitness (overall effect and moderating effect on the response to exercise) on glycaemic and insulinaemic responses to an ecologically valid, standardised meal in adolescents (n= 36 (16 girls), 11-13 years). The main findings were that postprandial insulin tAUC, following an ecologically valid lunch, was 70% lower in high-fit participants compared to low-fit (high-fit: 3785 pmol·L-1 x 120 min vs. low-fit: 6457 pmol·L-1 x 120 min, p = 0.002). Furthermore, the acute bout of football led to a 21% reduction in blood glucose concentration pre-lunch (football: 3.8 mmol·L- 1 vs. control: 4.6 mmol·L-1, p < 0.001). This study demonstrates that an acute bout of football reduces blood glucose concentration transiently following exercise, although the postprandial glycaemic and insulinaemic responses were not affected by exercise. Furthermore, these data support the findings of Chapter V demonstrating that postprandial insulin tAUC is lower in those with a higher physical fitness. The fourth experimental chapter (Chapter VII) examined the acute effects of the football activity (same participants as Chapter VI) and physical fitness on cognitive function and BDNF concentration in adolescents. The main findings were that response times were consistently quicker in high-fit adolescents, compared to their low-fit counterparts (executive function; high-fit: 960 ± 209 ms vs. low-fit: 1084 ± 243 ms, p < 0.001. working memory; high-fit: 761 ± 151 ms vs. low-fit: 834 ± 207 ms, p < 0.001). Additionally, the exercise-induced improvements in response times on a working memory task were exclusive to high-fit participants (football: 476 ± 85 ms vs. control: 507 ± 120 ms, p = 0.022). The present study was also the first to measure the timecourse of changes in BDNF concentrations post-exercise in adolescents, with no effect of exercise observed. Together, chapters VI and VII provide evidence of the potential benefits of games-based activity for both cardiometabolic health and cognition in adolescents. The final experimental chapter (Chapter VIII) examined the effects of a short-term (2 weeks) sprint-training intervention on risk factors for cardiometabolic disease and cognitive function in adolescent girls (n = 16, 11-12 years). The main findings were that 2 weeks of sprint training improved accuracy on a working memory task (adjusted between group difference; 2.0%, 95%CI [0.02, 3.9%], p = 0.046) and increased BDNF concentration (adjusted between group difference; 17.89 ng·ml-1, 95% CI [10.7, 25.1 ng·ml-1], p < 0.001) in adolescent girls. This is also the first study to assess the effect of chronic exercise training on markers of low-grade chronic inflammation and the postprandial response to a standardised meal in adolescent girls, which were not affected. In summary, the present thesis provides novel contributions to the literature with the following key findings: i) Physical fitness is crucial in reducing postprandial markers of cardiometabolic health and in enhancing response times during cognitive function tests in adolescents; ii) Adiposity is an important determinant of the magnitude of postprandial markers of metabolic health; iii) An acute bout of football - which is an ecologically valid mode of exercise that reflects the habitual activity patterns of young people - is successful at reducing blood glucose concentrations, as well as selectively improving working memory in those considered high-fit; iv) Although short-term sprint training did not improve markers of cardiometabolic health, the present thesis shows that it can improve cognitive function in adolescent girls; v) The present thesis also demonstrates the utility of new physical activity metrics (representing activity volume and intensity) in paediatric research, which have currently not been used in conjunction with a range of risk factors for cardiometabolic disease and cognitive function; vi) Finally, throughout this thesis physical fitness and adiposity were assessed using accessible, relatively non-invasive, methods (MSFT and waist circumference) and therefore highlight their utility and application in paediatric research. Overall, from the data presented in this thesis it is recommended that every effort is made to enhance physical fitness and to reduce adiposity in adolescents to enhance cardiometabolic health and to optimise cognitive function.
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