Aerobic exercise induced skeletal muscle MOTS-c secretion: A novel therapy for MASLD via hepatic ACE2 regulation
Abstract
Aerobic exercise is pivotal for managing metabolic dysfunction-associated steatotic liver disease (MASLD), but its mechanisms remain unclear. This study investigates the anti-MASLD effects of MOTS-c, a mitochondrial peptide secreted during aerobic exercise, in diabetic MASLD mice and HepG2 cells. Our study found MOTS-c expression in skeletal muscle was reduced in the MASLD mice but restored by aerobic exercise. Both MOTS-c and aerobic exercise significantly improved hepatic steatosis in MASLD mice by suppressing lipid synthesis and inflammation. MOTS-c’s protective effects were diminished in ACE2-knockout mice. The results revealed a synergistic reduction in pAMPK and ACE2 expression in the MASLD mice, partially reversible by MOTS-c intervention. In HepG2 cells, MOTS-c-induced hepatic ACE2 upregulation was counteracted by the AMPK inhibitor Compound C. These findings suggest that aerobic exercise-induced secretion of skeletal muscle MOTS-c ameliorates MASLD via hepatic ACE2 upregulation, providing a novel non-pharmacological target for metabolic liver diseases.
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BibTeX
@article{li2026aerobic,
title = {{Aerobic exercise induced skeletal muscle MOTS-c secretion: A novel therapy for MASLD via hepatic ACE2 regulation}},
author = {Rui Li and Fangyu Li and Qi Chen and Yuanyuan Gao and Zhuoying Wu and Hongjun Deng and Li Yuan},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-60273-8},
url = {https://www.nature.com/articles/s41598-026-60273-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Aerobic exercise induced skeletal muscle MOTS-c secretion: A novel therapy for MASLD via hepatic ACE2 regulation
AU - Rui Li
AU - Fangyu Li
AU - Qi Chen
AU - Yuanyuan Gao
AU - Zhuoying Wu
AU - Hongjun Deng
AU - Li Yuan
PY - 2026
DA - 2026/10/22
JO - Scientific Reports
DO - 10.1038/s41598-026-60273-8
UR - https://www.nature.com/articles/s41598-026-60273-8
AB - Aerobic exercise is pivotal for managing metabolic dysfunction-associated steatotic liver disease (MASLD), but its mechanisms remain unclear. This study investigates the anti-MASLD effects of MOTS-c, a mitochondrial peptide secreted during aerobic exercise, in diabetic MASLD mice and HepG2 cells. Our study found MOTS-c expression in skeletal muscle was reduced in the MASLD mice but restored by aerobic exercise. Both MOTS-c and aerobic exercise significantly improved hepatic steatosis in MASLD mice by suppressing lipid synthesis and inflammation. MOTS-c’s protective effects were diminished in ACE2-knockout mice. The results revealed a synergistic reduction in pAMPK and ACE2 expression in the MASLD mice, partially reversible by MOTS-c intervention. In HepG2 cells, MOTS-c-induced hepatic ACE2 upregulation was counteracted by the AMPK inhibitor Compound C. These findings suggest that aerobic exercise-induced secretion of skeletal muscle MOTS-c ameliorates MASLD via hepatic ACE2 upregulation, providing a novel non-pharmacological target for metabolic liver diseases.
SN - 2045-2322
ER -