The impact of mitokine MOTS-c administration on the soleus muscle of rats subjected to a 7-day hindlimb suspension.

The aim of the study was to investigate the effect of MOTS-c on the key functional alterations in the rat soleus muscle during 7-day unloading - the transformation of slow fibers into fast ones, atrophy and increased fatigue. We daily intraperitoneally injected male Wistar rats with a short mitochondrial peptide MOTS-c during 7-day unloading of their hind limbs. After the end of the experiment, we conducted an ex vivo fatigue test of soleus muscle and showed that the MOTS-c administration prevents increased fatigue during 7-day hind limb unloading. Also, using immunohistochemical analysis, we showed that MOTS-c prevents the transformation of slow fibers into fast ones, mitigates the slow muscle atrophy fibers (but not fast ones) of the soleus muscle. In the group receiving MOTS-c, the decrease in Akt and GSK3β phosphorylation was prevented, and the 18 S and 28 S rRNA levels were at the control level. The ubiquitin ligases MuRF and Atrogin-1 mRNA were also reduced compared to the hindlimb unloading group with placebo. In addition, MOTS-c prevented a decrease in the expression of a few mitochondrial biogenesis parameters and the level of ACC phosphorylation (AMPK target). Thus, the MOTS-C injections during hind limb unloading lead to the normalization of several protein synthesis and degradation processes and support the expression of genes that ensure muscle resistance to fatigue.