TY - JOUR
T1 - MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose
AU - Hyatt, Jon Philippe K.
N1 - Funding Information:
The author would like to thank Mr. Beau Pullman for technical help, husbandry, and insightful discussions.
Publisher Copyright:
© 2022 The Author. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
PY - 2022/7
Y1 - 2022/7
N2 - Skeletal muscle adapts to aerobic exercise training, in part, through fast-to-slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial-derived peptide, MOTS-c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS-c and exercise. Compared to sedentary controls, 4–8 weeks of voluntary running increased MOTS-c protein expression ~1.5-5-fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4–6 weeks of detraining. This MOTS-c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS-c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS-c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90-min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS-c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle-derived MOTS-c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS-c proteins levels.
AB - Skeletal muscle adapts to aerobic exercise training, in part, through fast-to-slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial-derived peptide, MOTS-c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS-c and exercise. Compared to sedentary controls, 4–8 weeks of voluntary running increased MOTS-c protein expression ~1.5-5-fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4–6 weeks of detraining. This MOTS-c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS-c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS-c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90-min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS-c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle-derived MOTS-c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS-c proteins levels.
KW - detraining
KW - medial gastrocnemius
KW - mouse
KW - plantaris
KW - rat
KW - tibialis anterior
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U2 - 10.14814/phy2.15377
DO - 10.14814/phy2.15377
M3 - Article
C2 - 35808870
AN - SCOPUS:85134045602
SN - 2051-817X
VL - 10
JO - Physiological reports
JF - Physiological reports
IS - 13
M1 - e15377
ER -