No abstract

Using a genetical metabolomics approach we assessed whether altered energy supply in locomoter muscle underlies the elevated aerobic performance of human genotypes containing a silencer region (I‐allele) of the major regulatory enzyme of vasoconstriction, angiotensin converting enzyme (ACE).Extensor muscle, m. vastus lateralis, of ACE‐II/ID genotypes holding the I‐allele demonstrated a trend for elevated capillarity compared to ACE‐DD counterparts lacking the I‐allele (311.0 vs. 279.7 mm‐2, n=20, p=0.10). In untrained subjects, maximal oxygen uptake during bicycle exercise was lower in ACE‐DD genotypes (44.9 vs. 47.8 ml O2/min/kg). Exhaustive aerobic exercise selectively reduced low density lipoproteins in serum of ACE‐II/ID genotypes (−14%) but was spared in ACE‐DD (+6%, p=0.25). By contrast, non‐polar metabolites in exercised muscle, comprising tentatively identified LDL‐derived glycerophosphocholine species, were depleted in ACE‐DD genotypes (q=2.8%; statistical analysis of microarrays). The interaction effect of exercise and genotype on lipidic muscle metabolites was maintained in trained subjects (p=0.03, ANOVA). The observations indicate that elevated import of serum lipids into exercised muscle underlies the enhanced aerobic exercise performance of I‐allelic genotypes for this major checkpoint of vascular perfusion.