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Integrative physiology of human aerobic fitness and the influence of the ACE I/Dp genotype

Vaughan, David (2013) Integrative physiology of human aerobic fitness and the influence of the ACE I/Dp genotype. Doctoral thesis (PhD), Manchester Metropolitan University.


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The search for genes that influence human performance and health constitutes a popular topic of current research. One such genetic constituent that has caused much interest over the last 20 years is the angiotensin converting enzyme insertion/deletion polymorphism (ACE I/Dp). There is much controversy in the literature regarding the role (if any) of this polymorphism as effects and effect size vary between populations of different origin and training status. The aim of this thesis was to analyse at the whole organism level whether skeletal muscle plasticity explains the association of the ACE I/D polymorphism with metabolic fitness. Regular endurance exercise reduces the risk of a plethora of diseases, but the exact molecular mechanisms are not fully understood – the ability of muscle to adapt to exercise stimulus is key. Trained individuals demonstrated clear physiological differences of aerobic processes such as increased oxygen usage, greater power output and reduced body fat that would be expected (T-Test: p<0.001). By contrast, when examining metabolite changes, at rest, in the local muscle there were few (n=6) nonpolar (lipid species) metabolite (assessed by mass spectrometry) differences between the trained and untrained. However, after an acute exercise bout working muscle in trained individuals displayed a significant up-regulation of (n=76) non-polar metabolites (Repeated ANOVA: p=0.0004), illustrating that training produces significant adaptations in substrate metabolism at the local level. Would there be a genetic component contributing towards these physiological and local muscle differences? Individuals with the ACE I-allele (insertion sequence) had increased capillary density, and there were significant differences in transcripts, together with both polar and non-polar metabolites in the untrained population at rest and following an acute exercise bout. These differences were lost in the trained population. In a different population (Swiss) capillary density was increased following a training programme in the absence of the I-allele – in contrast to the other population (British). However, gene expression response of important factors, to exercise was preserved. In conclusion, a trained population demonstrated enhanced non-polar metabolism in the working muscle after an exercise bout, and the dominant stimulus of regular exercise over-rides the influence of the ACE I/Dp. Nurture over-rides nature.

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