Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Effect of Resistance Training on the Expression of FOXO3, Murf1 and Mafbx Genes in the Soleus Muscle of Rats after 2 Weeks of Lower Limb Suspension

Document Type : Original Article(s)

Authors
Mohammad Manizadeh 1
Abdolreza Kazemi 2
Hamideh Abdolzadeh 3
Hossein Babaei 3
Vahid Ghanbari Mazidi 1
1 MSc of Sports Physiology, Department of Sports Sciences, Faculty of Literature and Human Sciences, Vali Asr University of Rafsanjan, Rafsanjan, Iran
2 Associated Professor, Department of Physical Education, Faculty of Letters and Humanities, Vali E-Asr University, Rafsanjan, Iran.
3 Assistant Professor, Department of Physical Education, Faculty of Letters and Humanities, Vali E-Asr University, Rafsanjan, Iran
10.48305/jims.v43.i818.0623
Abstract
Background: Long-term periods of inactivity or mechanical unloading can lead to significant loss of skeletal muscle mass and strength. In the present study, the effect of 4 weeks of resistance training on the expression changes of FOXO3, MuRF1 and MAFbx genes involved in muscle atrophy after a period of suspension in the soleus muscle of male rats was investigated.
Methods: Thirty-two male Wistar rats were randomly divided into four groups: suspended, retraining, detraining, and training. The training groups exercised 3 sessions per week for 4 weeks. Resistance training was performed by climbing a vertical ladder with a weight attached to the animals' tails. Forty-eight hours after the last training session, the soleus muscle was extracted and the gene expression levels were measured by Real-Time PCR technique. Data analysis was done with the difference between research variables was determined using one-way ANOVA tests and Tukey's post hoc test at a significance level of P ˂ 0.05.
Findings: The findings showed that the expression of FOXO3, MuRF1, and MAFbx genes significantly decreased due to resistance training in the soleus muscle of male rats, especially in the retraining group compared to other groups (P = 0.001, P = 0.001, and P = 0.001, respectively).
Conclusion: It seems that resistance training before and after lower limb suspension reduces atrophy in the soleus muscle of male rats, however, the retraining group is more resistant to atrophy. On the other hand, lower limb suspension increases the expression of atrophic genes (FOXO3, MuRF1 and MAFbx) in the soleus muscle of rats.

Highlights

Abdolreza Kazemi: Google Scholar

Keywords
Resistance training
Muscle atrophy
Gene expression

Subjects

  1. Madahi M, Gharakhanlou R, Kazemi A, Azarbayjani MA. Effect of Reduced Physical Activity on Murf-1 and Atrogin-1 Gene Expression in Soleus Muscle of Wistar Rats Following Endurance, Resistance and Combined Training. The Scientific Journal of Rehabilitation Medicine 2022; 11(2): 250-63.
  2. Chen K, Gao P, Li Z, Dai A, Yang M, Chen S, et al. Forkhead Box O signaling pathway in skeletal muscle atrophy. Am J Pathol 2022; 192(12): 1648-57.
  3. Kitajima Y, Yoshioka K, Suzuki N. The ubiquitin–proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders. J Physiol Sci 2020; 70(1): 40.
  4. Moradiani H, Zolfaghari MR, Khodaei K. Comparison of the efficacy of 12 Weeks of Resistance and Combined Training on Activation of AMPK Signaling and Gene Expression of Muscle Atrophy markers in Middle-Aged Women. Journal of Applied Health Studies in Sport Physiology 2024; 12(1).
  5. Sheikhan M, Kordi MR, Rajabi H. Effect of a Lower Limb Restless Period on Expression of Mir-1 and Mir-206 Neural Muscle Genes in Endurance Training Rats [in Persian]. J Arak Uni Med Sci 2020; 23(4): 570-9.
  6. Bae JH, Seo DY, Lee SH, Shin C, Jamrasi P, Han J, et al. Effects of exercise on AKT/PGC1-α/FOXO3a pathway and muscle atrophy in cisplatin-administered rat skeletal muscle. Korean J Physiol Pharmacol 2021; 25(6): 585-92.
  7. Moradi Y, Zehsaz F, Nourazar MA. 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): 21-7.
  8. Gao Y, Arfat Y, Wang H, Goswami N. Muscle atrophy induced by mechanical unloading: mechanisms and potential countermeasures. Front Physiol 2018; 9: 235.
  9. Zhang Z-K, Li J, Liu J, Guo B, Leung A, Zhang G, et al. Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading. Sci Rep 2016; 6(1): 20300.
  10. Kazemi A, Kerendi H, Khajehpour Z. Effect of Spinal Nerve Ligation after Endurance Training on the Gene Expression of MST1 and MAFbx in Plantaris Muscle of Male Wistar Rats [in Persian]. J Mazandaran Univ Med Sci 2022; 32(209): 1-12.
  11. Dungan CM, Murach KA, Frick KK, Jones SR, Crow SE, Englund DA, et al. Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining. Am J Physiol Cell Physiol 2019; 316(5): C649-C54.
  12. Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol (1985) 2002; 92(4): 1367-77.
  13. Kazremi A, Masoumpor Z, Dakhili A, Zangiabadi A, Fathi I. The Effect of mechanical unloading on TRAF6 and MuRF1 genes expression in soleus muscle of male Wistar rats [in Persian]. Journal of Sport and Exercise Physiology 2021; 13(2): 67-74.
  14. Rahmati M, Ghanbarzadeh M, Aghaei MH. The effect of decreased activity in the form of neuropathic pain on GSK-3 β gene expression in sciatic nerve fiber of male Wistar rats [in Persian]. Qom Univ Med Sci J 2018; 12(2): 11-8.
  15. Madahi M, Gharakhanlou R, Kazemi A, Azarbayjani MA. Effect of Reduced Physical Activity on Murf-1 and Atrogin-1 Gene Expression in Soleus Muscle of Wistar Rats Following Endurance, Resistance and Combined Training [in Persian]. Journal of Sport and Biomotor Sciences 2022; 11(2): 250-63.
  16. Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab 2014; 307(6): E469-E84.
  17. Kang S-H, Lee H-A, Kim M, Lee E, Sohn UD, Kim I. Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing’s syndrome. Am J Physiol Endocrinol Metab 2017; 312(6): E495-E507.
  18. Alizadeh Pahlavani H. Exercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors. Front Endocrinol (Lausanne) 2022; 13: 811751.
  19. Yoshida T, Delafontaine P. Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells 2020; 9(9): 1970.
  20. Jones SW, Hill RJ, Krasney PA, O'Conner B, Peirce N, Greenhaff PL. Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with the regulation of skeletal muscle mass. FASEB J 2004; 18(9): 1025-7.
  21. Azimian E, Akbarnejad Gharehloo A, Pournemati P. The effect of 8 weeks of resistance training on muscle function and some proteins related to sarcopenia in soleus muscle of obese aged male rats. Journal of Applied Health Studies in Sport Physiology 2023; 10(2): 13-26.
  22. Kohno S, Yamashita Y, Abe T, Hirasaka K, Oarada M, Ohno A, et al. Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages. J Appl Physiol (1985) 2012; 112(10): 1773-82.
  23. Wang Q, Hu J, Liu Y, Li J, Liu B, Li M, et al. Aerobic exercise improves synaptic-related proteins of diabetic rats by inhibiting FOXO1/NF-κB/NLRP3 inflammatory signaling pathway and ameliorating PI3K/Akt insulin signaling pathway. J Mol Neurosci 2019; 69(1): 28-38.
  24. Foreman NA, Hesse AS, Ji LL. Redox signaling and sarcopenia: searching for the primary suspect. Int J Mol Sci 2021; 22(16): 9045.
  25. Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol 2007; 292(1): C188-C99.
  26. Romanello V, Sandri M. Mitochondrial quality control and muscle mass maintenance. Front Physio 2016; 6: 422.
  27. Lessard SJ, MacDonald TL, Pathak P, Han MS, Coffey VG, Edge J, et al. JNK regulates muscle remodeling via myostatin/SMAD inhibition. Nat Commun 2018; 9(1): 3030.
  28. Bilet L, Phielix E, van de Weijer T, Gemmink A, Bosma M, Moonen-Kornips E, et al. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension. Diabetologia 2020; 63(6): 1211-22.
  29. Khaleghi I, Alijani E, Rahimi A, Mohsenzade M. Simultaneous effect of resistance training and endothelial ancestral cell injection on expression of MURF1 muscle degeneration factor and its relationship with insulin resistance in STZ-induced diabetic male rats [in Persian]. Iranian Journal of Diabetes and Metabolism 2021; 21(3): 175-85.
  30. Léger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, et al. Akt signalling through GSK‐3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 2006; 576(3): 923-33.
  31. Mousavi Mozafar SM, Nourshahi M, Akbarnejad A. Muscle Murf1 and P70S6K Before and After 6 Weeks of Resistance Training and HMB Supplementation in Inactive Men. Sport Physiology 2020; 12(45): 79-94.
  32. Lee JH, Jun H-S. Role of myokines in regulating skeletal muscle mass and function. Front Physiol 2019; 10: 42.
  33. Bruusgaard JC, Johansen I, Egner I, Rana Z, Gundersen K. Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proc Natl Acad Sci U S A 2010; 107(34): 15111-6.
  34. Murach KA, Mobley CB, Zdunek CJ, Frick KK, Jones SR, McCarthy JJ, et al. Muscle memory: myonuclear accretion, maintenance, morphology, and miRNA levels with training and detraining in adult mice. J Cachexia Sarcopenia Muscle 2020; 11(6): 1705-22.

Seaborne RA, Strauss J, Cocks M, Shepherd S, O’Brien TD, van Someren KA, et al. Human skeletal muscle possesses an epigenetic memory of hypertrophy. Sci Rep 2018; 8(1): 1898.

Journal of Isfahan Medical School
Volume 43, Issue 818
2nd Week, August
July and August 2025
Pages 623-631

  • Receive Date 12 November 2024
  • Accept Date 01 June 2025