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