Different effects of 3-week disuse on the phenotype and gene expression of the calf and thigh muscles

Disuse, like several other pathological conditions, has specific effects on various skeletal muscles; the mechanisms underlying these responses remain unclear. We aimed to compare the disuse-induced changes in the phenotype and proteome of the calf and thigh muscles, and to assess the extent to which these proteomic changes are regulated at the mRNA and other levels. Twelve healthy young males participated in 3-week bed rest. Disuse resulted in a greater decrease in lean mass, aerobic performance, and changes in the proteome and transcriptome of the calf muscles/m. soleus than the thigh muscles/m. vastus lateralis. A greater decrease in calf muscle mass was related to a decrease in the expression/deactivation of translation regulators, but not to the expression of the main sarcomeric proteins. At the same time, a significant decrease in aerobic performance of the ankle plantar flexors occurred without changing the expression of oxidative enzymes - a marker of mitochondrial density. That decrease was associated with dysregulation of mitochondrial biogenesis. Most large-scale changes in the transcriptome did not translate into changes in the proteome, suggesting a redundancy in regulation at the mRNA levels. However, changes in the RNA levels were revealed to play a dominant role in regulating specific proteins, whereas for others, this factor played little or no role. In conclusion, our findings partially explain why calf muscles with a strong postural function are more sensitive to short-term disuse. This provides a foundation for developing targeted approaches to counteract the negative effects of disuse on different muscles.