Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


Associate Prof, Dept of Physical Education, Faculty of Letters and Humanities, Vali E Asr University, Rafsanjan, Iran.


Decreasing muscle mass is one of the detraining characteristics that associated with attenuated in muscle strength and muscle performance, and resulting in disability in performing of daily tasks. The purpose of the present study was to investigate the effect of decreased physical activity in the form of chronic constriction injury (CCI) on the Tweak and Fn14 proteins after resistance, endurance and combined exercises. 32 rats were randomly divided into four groups: 1- Control group-CCI (Sham+CCI), 2- Mixed training group-CCI (Mix+CCI), 3- Endurance training group-CCI (TE+CCI), and 4- Resistance training group-CCI (LA+CCI). Mix+CCI, TE+CCI and CCI+SNL groups participated in training program for six weeks. After performing 6 weeks training, chronic constriction injury was implemented for four weeks. Western blotting technique was used to measure proteins. The results extracted by ANOVA and showed that Tweak and Fn14 proteins increased by CCI. The level of Tweak and Fn14 proteins in CCI+La and CCI+Mix groups and also CCI-TE group was significantly lower than Sham+CCI group (P <0.05). One the other hands, the level of Fn14 protein in CCI-LA compared with CCI-TE and CCI-MIX was not significant (P >0.05). According to the findings of the present study, it seems that mice that had resistance training in their training program experienced less atrophy than the group that did only endurance training.


Main Subjects


    1. Jespersen, J., Nedergaard, A., Andersen, L., Schjerling, P. & Andersen, J. 2011. Myostatin Expression during Human Muscle Hypertrophy and Subsequent Atrophy: Increased Myostatin with Detraining Scand J Med Sci Sports. ;21(2):215-23.
    2. Paul PK1, Gupta SKBhatnagar SPanguluri SKDarnay BGChoi Y, et al. 2010. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol. 191(7):1395-411.
    3. Glass, D.J., Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nature cell biology, 2003. 5(2): p. 87-90.
    4. Hu, G., W. Zeng, and Y. Xia, TWEAK/Fn14 signaling in tumors. Tumor Biology, 2017. 39(6): p. 1010428317714624.
    5. Kumar, A., S. Bhatnagar, and P.K. Paul, TWEAK and TRAF6 regulate skeletal muscle atrophy. Current opinion in clinical nutrition and metabolic care, 2012. 15(3): p. 233.
    6. Dogra, C., et al., Fibroblast Growth Factor Inducible 14 (Fn14) Is Required for the Expression of Myogenic Regulatory Factors and Differentiation of Myoblasts into Myotubes EVIDENCE FOR TWEAK-INDEPENDENT FUNCTIONS OF Fn14 DURING MYOGENESIS. Journal of Biological Chemistry, 2007. 282(20): p. 15000-15010.
    7. Dogra, C., et al., Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-κB and degradation of MyoD protein. Journal of Biological Chemistry, 2006. 281(15): p. 10327-10336.
    8. Peterson, J.M., N. Bakkar, and D.C. Guttridge, NF-κB signaling in skeletal muscle health and disease, in Current topics in developmental biology. 2011, Elsevier. p. 85-119.
    9. Kumar, A., et al., TWEAK/Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy. 2010, Federation of American Societies for Experimental Biology.
    10. Clarke, B.A., et al., The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle. Cell metabolism, 2007. 6(5): p. 376-385.
    11. Sheffield-Moore, M., et al., Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. American Journal of Physiology-Endocrinology and Metabolism, 2004. 287(3): p. E513-E522.
    12. Cunha, T.F., et al., Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure. PloS one, 2012. 7(8): p. e41701.
    13. Shefer, G., et al., Reduced satellite cell numbers and myogenic capacity in aging can be alleviated by endurance exercise. PloS one, 2010. 5(10): p. e13307.
    14. Gibala, M.J., et al., Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. The Journal of physiology, 2006. 575(3): p. 901-911.
    15. Malmberg, A.B. and A.I. Basbaum, Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain, 1998. 76(1-2): p. 215-222.
    16. Chae, C.-H. and H.-T. Kim, Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochemistry international, 2009. 55(4): p. 208-213.
    17. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Cardiovascular Prevention & Rehabilitation. 2007;14(6):753-60
    18. Lee, S. and R.P. Farrar, Resistance training induces muscle-specific changes in muscle mass and function in rat. Journal of Exercise physiology online, 2003. 6(2).
    19. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87-107, doi: 10.1016/0304-3959(88)90209-6.
    20. Rahmati M, Kazemi A. Various exercise intensities differentially regulate GAP-43 and CAP-1 expression in the rat hippocampus.2019 GENE; 15(692): 185-94.
    21. Nilwik, R., Snijders, T., Leenders, M., Groen, B. B., Van Kranenburg, J., Verdijk, L. B. & Van Loon, L. J. 2013. The Decline In Skeletal Muscle Mass With Aging Is Mainly Attributed To A Reduction In Type Ii Muscle Fiber Size. Experimental Gerontology. 48, 492-498
    22. Muller, F. L., Song, W., Jang, Y. C., Liu, Y., Sabia, M., Richardson, A. & Van Remmen, H. Denervation-Induced Skeletal Muscle Atrophy Is Associated With Increased Mitochondrial Ros Production. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007; 293, R1159-R1168.
    23. Rowan, S. L., Rygiel, K., Purves-Smith, F. M., Solbak, N. M., Turnbull, D. M. & Hepple, R. T. 2012. Denervation Causes Fiber Atrophy and Myosin Heavy Chain Co-Expression in Senescent Skeletal Muscle. Plos One; 7, E29082.
    24. Verdijk, L.B., et al. 2007. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderlyAmerican Journal of Physiology-Endocrinology and Metabolism; 292(1): p. E151-E157.
    25. Bonaldo, P. & Sandri, M. Cellular and Molecular Mechanisms of Muscle Atrophy. Disease Models & Mechanisms, 2013; 6, 25-39
    26. Mittal, A., et al., The TWEAK–Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice. Journal of Cell Biology, 2010. 188(6): p. 833-849.
    27. Kazemi, A. and E. Jahanshahi, Effect of Spinal Nerve Ligation on The Expression of Tweak and Fn14 Genes in EDL Mucsle of Wistar Rats After HIT Training.
    28. Tajrishi, M.M., et al., The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle. Biochemical and biophysical research communications, 2014. 446(4): p. 1219-1224.
    29. Welle, S., S. Totterman, and C. Thornton, Effect of age on muscle hypertrophy induced by resistance training. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 1996. 51(6): p. M270-M275.
    30. Ribeiro, M.B.T., et al., Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats. Scientific reports, 2017. 7(1): p. 1-13.
    31. Moradi, Y., F. Zehsaz, and M.A. Nourazar, Concurrent exercise training and Murf-l and Atrogin-1 gene expression in the vastus lateralis muscle of male Wistar rats. Apunts Sports Medicine, 2020. 55(205): p. 21-27.
    32. Walton, R.G., et al., Human skeletal muscle macrophages increase following cycle training and are associated with adaptations that may facilitate growth. Scientific reports, 2019. 9(1): p. 1-14.
    33. Schönbauer, R., et al., Regular Training Increases sTWEAK and Its Decoy Receptor sCD163–Does Training Trigger the sTWEAK/sCD163-Axis to Induce an Anti-Inflammatory Effect? Journal of clinical medicine, 2020. 9(6):