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
Published Date:

Abstract

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, , in 18 untrained and 34 endurance-trained (physically active, [Formula: see text]O2max > 50 mL min kg) 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 and mean CSA of slow type fibers, which correlated with peak power output ( ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration ( = 0.016), ACE transcript levels ( = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise ( = 0.064). Capillary density ( = 0.001), capillary-to-fiber ratio ( = 0.010), systolic blood pressure ( = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF ( = 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.

Authors

  • Paola Valdivieso
    Laboratory for Muscle Plasticity, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
  • David Vaughan
    The Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
  • Endre Laczko
    Functional Genomics Center Zurich, ETH, University of Zurich, Zurich, Switzerland.
  • Michael Brogioli
    The Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
  • Sarah Waldron
    The Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
  • Jörn Rittweger
    The Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom.
  • Martin Flück
    Laboratory for Muscle Plasticity, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.

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