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

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, m. vastus lateralis, in 18 untrained and 34 endurance-trained (physically active,VO2max > 50 mL min −1 kg −1 ) 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 m. vastus lateralis and mean CSA of slow type fibers, which correlated with peak power output (r ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration (p = 0.016), ACE transcript levels (p = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise (p = 0.064). Capillary density (p = 0.001), capillary-to-fiber ratio (p = 0.010), systolic blood pressure (p = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF (p = 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.

Reactive Jumps Preserve Skeletal Muscle Structure, Phenotype, and Myofiber Oxidative Capacity in Bed Rest

“…Notably, the still incompletely understood microvascular network tissue changes during bed rest disuse in human skeletal muscle apparently seem to undergo time-dependent adaptation mechanisms (short-vs. long-term), for example, by intramuscular vascular signaling mechanisms, such as proposed for nitric oxide (NO) (Percival et al, 2010) controlled by mechanotransduction and mechanical loading as, for example, reflected by earlier studies investigating effects of short-duration, high-intensity exercises (high-intensity intermittent training (HIT), such as sprint and strength training, where consistent adaptation in capillarity was also not found (Tesch et al, 1984;Lüthi et al, 1986;Hoier et al, 2013;Gliemann, 2016;MacInnis and Gibala, 2017). With repetitive exercise, the consequent elevation in microvascular shear stress stimulates in conjunction with abluminal mechanical factors, morphogenic adaptations, and proliferation of endothelial cells in muscle capillaries (Bassett and Howley, 2000;Gustafsson and Kraus, 2001;Prior et al, 2003;Valdivieso et al, 2017), which may explain similar mechanisms to occur in bed rest exercise protocols. A limited number of studies in animals and humans have determined the presence of angiogenic factors in skeletal muscle at the gene and protein level in association with acute exercise and training (Breen et al, 1996;Lloyd et al, 2003;Rullman et al, 2007).…”

“…The optical density (OD) of the mitochondrial SDH histochemical stain on cryosections is a measure of the mass-specific maximal oxygen consumption of a fiber and was analyzed on freshly prepared biopsy cryosections (van der Laarse et al, 1989;Wüst et al, 2009;Bosutti et al, 2015). Briefly, an 8 µm thick serially cut section adjacent to the PECAM capillary-immunostained section was incubated at 37 • C in the dark for 45 min in 37 mM sodium phosphate buffer pH 7.6 with 74 mM sodium succinate and 0.4 mM tetra-nitroblue-tetrazolium.…”

“…The reaction was stopped with 0.01 N HCl (5 s) with water. Wet sections were mounted in glycerol gelatin (van der Laarse et al, 1989;Bosutti et al, 2015). Photomicrographs of stained cross sections were then captured, and the OD SDH of a fiber was determined by measuring the absorbance of the final reaction product (precipitate) using an interference filter at 660 nm (van der Laarse et al, 1989;Bosutti et al, 2015).…”

“…Wet sections were mounted in glycerol gelatin (van der Laarse et al, 1989;Bosutti et al, 2015). Photomicrographs of stained cross sections were then captured, and the OD SDH of a fiber was determined by measuring the absorbance of the final reaction product (precipitate) using an interference filter at 660 nm (van der Laarse et al, 1989;Bosutti et al, 2015). Absorbance was converted to OD by a calibration curve specific for each individual section created with a set of filters with known OD (ImageJ software) to minimize bias related to differences in lighting and precipitation rates.…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…Remarkably, there is a strict connection between genotype and phenotype in gene polymorphism for structural proteins and angiotensin-converting enzyme (ACE) [131]. This connection is particularly evident in differences between endurance or power muscles in athletes influencing sports performance, degree of vascularization, and mitochondria1 function [132].…”