Moderate Effects of Hypoxic Training at Low and Supramaximal Intensities on Skeletal Muscle Metabolic Gene Expression in Mice

Abstract

The muscle molecular adaptations to different exercise intensities in combination with hypoxia are not well understood. This study investigated the effect of low- and supramaximal-intensity hypoxic training on muscle metabolic gene expression in mice. C57BL/6 mice were divided into two groups: sedentary and training. Training consisted of 4 weeks at low or supramaximal intensity, either in normoxia or hypoxia (FiO2 = 0.13). The expression levels of genes involved in the hypoxia signaling pathway (Hif1a and Vegfa), the metabolism of glucose (Gys1, Glut4, Hk2, Pfk, and Pkm1), lactate (Ldha, Mct1, Mct4, Pdh, and Pdk4) and lipid (Cd36, Fabp3, Ucp2, Hsl, and Mcad), and mitochondrial energy metabolism and biogenesis (mtNd1, mtNd6, CytC, CytB, Pgc1a, Pgc1β, Nrf1, Tfam, and Cs) were determined in the gastrocnemius muscle. No physical performance improvement was observed between groups. In normoxia, supramaximal intensity training caused upregulation of major genes involved in the transport of glucose and lactate, fatty acid oxidation, and mitochondrial biogenesis, while low intensity training had a minor effect. The exposure to hypoxia changed the expression of some genes in the sedentary mice but had a moderate effect in trained mice compared to respective normoxic mice. In hypoxic groups, low-intensity training increased the mRNA levels of Mcad and Cs, while supramaximal intensity training decreased the mRNA levels of Mct1 and Mct4. The results indicate that hypoxic training, regardless of exercise intensity, has a moderate effect on muscle metabolic gene expression in healthy mice.

BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy

“…Paradigms of chronic intermittent hypoxia (mirroring sleep apnoea and respiratory diseases) must clearly be avoided given their deleterious effects on skeletal muscle function (Attaway et al., 2023; Drummond et al., 2022; 2023; O'Halloran, 2016; O'Halloran & Lewis, 2017). However, hypoxia‐dependent muscle metabolic reprogramming and angiogenesis (Clanton & Klawitter, 2001; Drozdovska et al., 2023; Li et al., 2020; Rizo‐Roca et al., 2018; Suzuki, 2016) could plausibly confer benefit to dystrophic respiratory muscles, with consequences for system performance. A body of work is required to establish the effects of AIH paradigms on respiratory muscle.…”