Distinct patterns of skeletal muscle wasting and mitochondrial changes following hypoxia and inflammation: associations with physiological phenotype
Skeletal muscle demonstrates a high degree of plasticity that may enable mitochondrial and protein turnover adaptations to environmental stressors such as hypoxia and inflammation. However, the effects of these stressors on skeletal muscle mitochondrial function and proteostatic pathways remain incompletely understood and may depend on muscle phenotype. Given the potential heterogeneity in skeletal muscle responses to these stressors, this study investigated their independent and combined effects on mitochondrial function and protein turnover pathways in oxidative soleus and glycolytic plantaris and assessed the consistency of these responses by comparison with a previous cohort. Adult male Wistar rats were exposed for four weeks to normobaric hypoxia and/or lipopolysaccharide-induced pulmonary inflammation. Mitochondrial respiration, enzymatic activities, markers of mitochondrial function and protein turnover and spontaneous locomotor activity (SLA) were assessed. Pulmonary inflammation predominantly affected soleus, triggering atrophy alongside impaired CI-dependent mitochondrial function, without changes in mitochondrial density. In contrast, plantaris exhibited only atrophy with no mitochondrial alterations in response to inflammation. Hypoxia induced atrophy selectively in plantaris. Notably, the changes following exposure to inflammation and/or hypoxia occurred independently of SLA alterations while the combination of these two stressors did not produce additive effects for most parameters. Comparison with our previous cohort revealed divergent responses that may have been influenced by differences in several physiological characteristics between the two cohorts. These findings demonstrate that hypoxia and pulmonary inflammation induce muscle-specific adaptations and suggest that physiological heterogeneity may contribute to variability in skeletal muscle vulnerability to chronic stress.