Exercise-intensity dependent variability in rates of aerobic metabolism is related to genetic aspects of muscle-type associated lactate transport in tactical athletes

Introduction: Lactate accumulation during exercise marks a shift toward anaerobic glucose metabolism when oxygen-dependent substrate metabolization cannot sustain repeated contraction. Thereby it may influence perfusion via dilation of resistance vessels and modulate ventilation through chemoreceptor activity, potentially contributing to interindividual variability in respiration, perfusion, and pulmonary oxygen uptake at metabolic thresholds. Genetic mechanisms further shape these processes: monocarboxylate transporter 1 (MCT1) enables lactate transport between fibers and tissues, while angiotensin converting enzyme (ACE) affects cardiovascular adaptation and metabolite redistribution (Gasser et al., 2024). Lactate accumulation at ventilatory thresholds correlates with haemoglobin deoxygenation in active muscle (Perrey et al., 2024; Batterson et al., 2023). These insights suggest genotype‑dependent regulation of lactate handling and aerobic fitness may drive variability in muscle oxygenation and systemic metabolism at exercise thresholds. Purpose: To investigate whether the MCT1 genotype influences relative rates of muscle and systemic aerobic metabolism at ventilatory thresholds (VT1, VT2) during exhaustive running, in interaction with ACE-ID genotype and aerobic fitness. Methods: A cohort of 169 Caucasian tactical athletes (27.7 ± 7.3 years; 179.2 ± 7.2 cm; 78.7 ± 10.2 kg) performed ramped, loaded treadmill exercise to exhaustion (Flück et al 2024). Aerobic metabolism was assessed via ergospirometry and near infrared spectroscopy in knee extensor (vastus lateralis, VAS) and ankle extensor (gastrocnemius medialis, GAS). Maximal oxygen uptake (VO₂max) and ventilatory thresholds were determined, with aerobic fitness defined as ≥50 mL O₂·min⁻¹·kg⁻¹. Genotyping of MCT1 (rs1049434) and ACE-ID (rs1799752) was performed using PCR. Effects of genotype, fitness, and muscle type were analyzed with ANOVA at a 5%-threshold. Results: Athletes demonstrated exceptional aerobic performance (510.4 ± 76.9 W) and VO₂max (4.2 ± 0.6 mL O₂·min⁻¹·kg⁻¹). Blood lactate concentration increased in post exercise (η²=0.033) but was unaffected by MCT1 genotype (p=0.256) or aerobic fitness (p=0.930). Muscle oxygen saturation (SmO₂) in VAS decreased markedly with exercise intensity (63.9% to 15.0% at VO₂max), influenced by MCT1 (η²=0.01) and ACE genotype (η²=0.013), but independent of aerobic fitness. Haemoglobin concentration (tHb) in VAS muscle remained relatively stable (11.57–12.92 g·L⁻¹), yet varied with aerobic fitness (η²=0.094) and its interactions with MCT1 (p=0.021, η²=0.039) and ACE-ID (η²=0.037). Fractional power output at VT1 depended on aerobic fitness (η²=0.115), but not genotype. VO₂max-rated fractional deoxygenation of VAS and GAS at VT1 (η²=0.036), but not VT2, was associated with MCT1, further interacting with ACE ID (η²=0.085) and aerobic fitness (η²=0.041). Strong VT1-specific associations were observed for haemoglobin-related deoxygenation in VAS with MCT1 (η²=0.125), MCT1 × ACE ID (η²=0.066), and MCT1 × fitness (η²=0.062). The VAS–GAS oxygenation ratio at VT1 was influenced by MCT1 (η²=0.029), ACE ID (η²=0.069), and fitness (η²=0.035), with all factors interacting; this effect disappeared at VT2 and VO₂max. Fractional muscle deoxygenation was highest in AT-genotypes of rs1049434 (Figure 1). Conclusion: MCT1 and ACE genotypes, together with aerobic fitness, jointly influence intramuscular coordination of aerobic metabolism—though not perfusion—at VT1, the point of lactate accumulation consistent with rs1049434–T–allele–related slow fiber composition (Gasser et al., 2024). Discussion: Metabolic intensity-related and genotype‑dependent variability in muscle deoxygenation, underscores implications for personalized training aimed at anaerobic reserves. References: Gasser, B., Dössegger A., Giraud M.N. & Flück M. (2024). T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise. Genes (Basel) 15(7), 918. https://doi.org/10.3390/genes15070918. Perrey S., Quaresima V. & Ferrari M. (2024). Muscle Oximetry in Sports Science: An Updated Systematic Review. Sports Medicine, 54(4), 975-996. https://doi.org/10.1007/s40279-023-01987-x. Batterson P.M., Kirby B.S., Hasselmann G. & Feldmann A. (2023). Muscle oxygen saturation rates coincide with lactate-based exercise thresholds. European Journal of Applied Physiology, 123(10), 2249-2258. https://doi.org/10.1007/s00421-023-05238-9. Flück M., Protte C., Giraud M.N. Gsponer T. & Dössegger A. (2024). Genotypic Influences on Actuators of Aerobic Performance in Tactical Athletes. Genes (Basel), 15(12), 1535. https://doi.org/10.3390/genes15121535.