Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization

Purpose: Heat stress, like exercise, can elicit beneficial mitochondrial adaptations and attenuate disuse muscle atrophy. The beneficial effects of heat therapy may in part be related to mitokines as they are released by the cells in response to perceived mitochondrial stress. This study thus investigated the effect of repeated heat exposures on mitokine response in the context of immobilization-induced muscle atrophy. Methods: A total of 19 physically active men underwent 4 weeks of supervised training followed by 2 weeks of immobilization of the left ankle, during which they were randomly divided into the heat (n = 9) or the sham (n = 10) treatment group. Muscle thickness by ultrasound, cross sectional area by magnetic resonance imaging, circulating and skeletal muscle mitokine levels, as well as a series of skeletal muscle anabolism and atrophy markers were assessed before and after the 2-week immobilization period. Results: While immobilization did not induce any effect on mitokine levels, repeated heat treatment upregulated the circulating MOTS-c (p = 0.033) and downregulated the skeletal muscle FGF21 (p = 0.027) levels. Immobilization decreased muscle thickness (p = 0.012, η² = 0.32) and cross-sectional area (CSA, p < 0.01, η² = 0.75) of the gastrocnemius medialis. Conclusions: our results indicate that repeated heat stress specifically modulates the levels of the mitokines MOTS-c and FGF21 in a manner that is comparable to, but not identical to, exercise. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic potential of heat stress and mitokines in mitigating muscle loss.