AUTHOR=Valdivieso Paola , Vaughan David , Laczko Endre , Brogioli Michael , Waldron Sarah , Rittweger Jörn , Flück Martin 

TITLE=The Metabolic Response of Skeletal Muscle to Endurance Exercise Is Modified by the ACE-I/D Gene Polymorphism and Training State

JOURNAL=Frontiers in Physiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00993

DOI=10.3389/fphys.2017.00993

ISSN=1664-042X

ABSTRACT=<p>The insertion/deletion polymorphism in the gene for the regulator of vascular tone, angiotensin-converting enzyme (ACE), is the prototype of a genetic influence on physical fitness and this involves an influence on capillary supply lines and dependent aerobic metabolism in skeletal muscle. The respective interaction of ACE-I/D genotype and training status on local metabolic and angiogenic reactions in exercised muscle is not known. Toward this end we characterized the metabolomic and angiogenic response in knee extensor muscle, <italic>m. vastus lateralis</italic>, in 18 untrained and 34 endurance-trained (physically active, <inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mover accent="true"><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:math></inline-formula>O2max &gt; 50 mL min<sup>−1</sup> kg<sup>−1</sup>) white British men to an exhaustive bout of one-legged cycling exercise. We hypothesized that training status and ACE-I/D genotype affect supply-related muscle characteristics of exercise performance in correspondence to ACE expression and angiotensin 2 levels. ACE-I/D genotype and training status developed an interaction effect on the cross-sectional area (CSA) of <italic>m. vastus lateralis</italic> and mean CSA of slow type fibers, which correlated with peak power output (<italic>r</italic> ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration (<italic>p</italic> = 0.016), ACE transcript levels (<italic>p</italic> = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise (<italic>p</italic> = 0.064). Capillary density (<italic>p</italic> = 0.001), capillary-to-fiber ratio (<italic>p</italic> = 0.010), systolic blood pressure (<italic>p</italic> = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF (<italic>p</italic> = 0.043) depended on the ACE-I/D genotype alone. Our observations indicate that variability in aerobic performance in the studied subjects was in part reflected by an ACE-I/D-genotype-modulated metabolic phenotype of a major locomotor muscle. Repeated endurance exercise appeared to override this genetic influence in skeletal muscle by altering the ACE-related metabolic response and molecular aspects of the angiogenic response to endurance exercise.</p>