Identification of Potentially Related Genes and Mechanisms Involved in Skeletal Muscle Atrophy Induced by Excessive Exercise in Zebrafish

• Published in: Biology (Basel, Switzerland) Switzerland), 2021-08, Vol.10 (8), p.761
• Main Authors: Sun, Chen-Chen, Zhou, Zuo-Qiong, Chen, Zhang-Lin, Zhu, Run-Kang, Yang, Dong, Peng, Xi-Yang, Zheng, Lan, Tang, Chang-Fa
• Format: Article
• Language: English
• Subjects: Adaptation; Antibodies; Apoptosis; Atrophy; Autophagy; Circadian rhythms; Danio rerio; excessive exercise; Experiments; Fatigue; Forkhead protein; FoxO signaling pathway; Genes; Genetic engineering; Genomes; Homeostasis; Hsp70 protein; Hypertrophy; Insulin-like growth factor II receptors; MDM2 protein; Musculoskeletal system; Online data bases; Ontology; Overtraining; Oxidative stress; Oxygen consumption; p53 Protein; p53 signaling pathway; Pathogenesis; Period 3 protein; Phagocytosis; Physical training; Physiology; Proteins; Signal transduction; Skeletal muscle; skeletal muscle atrophy; Software; Statistical analysis; Velocity; Wnt signaling pathway
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology10080761

Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein–protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.