The Effect of Exposure to Hypoxia during Resistance Training on the Concentration of PAX7 and PGC-1α Proteins in Fast-Twitch Muscle Tissue of Diabetic Rats Fed a High-Fat Diet

Document Type : Research Paper

Authors

1 PhD Student of Sports Physiology, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran.

2 Sports Physiology Department, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran.

3 Sports Physiology Department, South Tehran Branch, Islamic Azad University, Tehran, Iran.

Abstract

Introduction: Myopathy caused by diabetes can accelerate the disease process in diabetic people. Myopathy has important indicators in muscle tissue related to regeneration and intracellular metabolism in skeletal muscles. The current study aimed to evaluate the effect of eight weeks of resistance training in hypoxia on the content of PAX 7 and PGC-1α proteins in the gastrocnemius muscle of type 2 diabetic rats. Methods: This experimental study was conducted on 24 male Wistar rats for six weeks after induction of type 2 diabetes. Rats were divided into three groups: healthy control (HC), diabetic control (DC), and hypoxia group (HPX). Resistance training was applied for eight weeks under oxygen deficiency conditions in the groups of resistance training in hypoxia. The tissue sample was taken from the biceps muscle after finishing the exercises and evaluated to measure the concentration of PAX7 and PGC-1α proteins. The results were analyzed by one-way analysis of variance at a significance level α ≤0.05. Results: There was a significant difference in PAX7 and PGC-1α proteins between the research groups (P=0.0001). Induction of diabetes led to a significant decrease in PAX7 compared to the control group. PGC1-α protein levels also decreased significantly in the diabetes induction group compared to the control group (P=0.0001). However, exposure to hypoxia did not change the gene expression values of this variable compared to the diabetic patient group (P=0.451). Conclusion: Exposure to temporary and passive hypoxia can be considered as a suggested strategy to improve indicators related to type 2 diabetes in humans.

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  1. Sergi D, Naumovski N, Heilbronn LK, Abeywardena M, O’Callaghan N, Lionetti L and Luscombe-Marsh N. Mitochondrial (Dys) function and Insulin Resistance: from pathophysiological molecular mechanisms to the impact of Front Physiol 2019; 10:532.
  2. Bazgir B, asgari A. The Interactive role of exercise and satellite cells in skeletal muscle regeneration and hypertrophy. EBNESINA. 2015; 16 (4) :47-63
  3. Went Y, Bi P, Liu W, Asakura A, Keller C, Kuang S. Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Molecular and Cellular Biology. 2012; 32(12):2300-11.
  4. Evans PL, McMillin SL, Weyrauch LA, & Witczak CA. Regulation of skeletal muscle glucose transport and glucose metabolism by exercise training. Nutrients. 2019; 11(10), 2432.
  5. Li J, Li Y, Atakan MM, Kuang J, Hu Y, Bishop DJ, Yan X. The molecular adaptive responses of skeletal muscle to high-intensity exercise/training and hypoxia. Antioxidants. 2020; 9(8):656.
  6. Nguyen TH, Conotte S, Belayew A, Declèves AE, Legrand A, Tassin A. Hypoxia and hypoxia-inducible factor signaling in muscular dystrophies: cause and consequences. International Journal of Molecular Sciences. 2021; 22(13), 7220.
  7. Nishimura A, Sugita M, Kato K, Fukuda A, Sudo A, Uchida A. Hypoxia increases muscle hypertrophy induced by resistance training. Int J Sports Physiol Perform. 2010; 5(4):497-508.
  8. Fan W, Evans R. PPARs and ERRs: Molecular mediators of mitochondrial metabolism. Curr Opin Cell Biol. 2015; 33: 49–54.
  9. Krako Jakovljevic N, Pavlovic K, Jotic A, Lalic, K, Stoiljkovic M, Lukic L, Milicic T, Macesic M, Stanarcic Gajovic J, Lalic NM. Targeting mitochondria in Int J Mol Sci. 2021; 22, 6642.
  10. Gaster M, Rustan AC, Aas V, Beck-Nielsen H. Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin: Evidence from cultured myotubes. Diabetes. 2004; 53:542–8.
  11. FallahpourNooshabadi S, Kazemzadeh Y, Gorzi A. The effect of eight weeks of daily normobaric hypoxia (60 minutes) on PGC­1α content of soleus muscle, insulin resistance, and fasting glucose in type 2 diabetic rats. Ebnesina. 2021; 22 (4):89-94.
  12. Tashakori Zade, M, Mogharnasi M. A Study of the Effect of 10 Weeks of Resistance Training on HSP70 and Insulin Resistance in Type 2 Diabetic Women. Journal of Sport Biosciences. 2016; 8(3): 341-351.
  13. Faramoushi M, Amir Sasan R, Vahid S S, Karimi P. Effect of simulated intermittent altitude on the metabolic and hematologic parameters in streptozotocin induced diabetic rats. J Ardabil Univ Med Sci. 2016; 16 (1):53-64.
  14. Woolcott OO, Ader M, Bergman RN. Glucose homeostasis during short-term and prolonged exposure to high altitudes. Endocrine Reviews. 2015; 36(2), 149–73.
  15. Fujimaki, Shin, Tomoko Kuwabara. "Diabetes-induced dysfunction of mitochondria and stem cells in skeletal muscle and the nervous system. International Journal of Molecular Sciences. 2017; 18(10): 2147.
  16. Bachman JF, Klose A, Liu W, Paris ND, Blanc RS, Schmalz M, Knapp E, Chakkalakal JV. Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution. Development. 2018; 145(20): dev167197.
  17. Krause MP, Al-Sajee D, D’Souza DM, Rebalka IA, Moradi J, Riddell MC, Hawke TJ. Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle. PLoS ONE. 2013; 8: e70971.
  18. Oberbach A, Bossenz Y, Lehmann S, Niebauer J, Adams V, Paschke R, Schon MR, Bluher M, Punkt K. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care. 2006; 29: 895–900.
  19. Kamei D, Yamakawa K, Takegoshi Y, Mikami-Nakanishi M, Nakatani Y, Oh-Ishi S, Yasui H, Azuma Y, Hirasawa N, Ohuchi K, Kawaguchi H, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Kudo I. Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin e synthase-1. J Biol Chem. 2004; 279(32):33684-95.
  20. Ruas JL, White JP, Rao RR, Kleiner S, Brannan, KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, & Spiegelman B M. A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell. 2012; 151(6), 1319–31.
  21. Britto FA, Gnimassou O, De Groote E, Balan E, Warnier G, Everard A, Cani PD, Deldicque L. Acute environmental hypoxia potentiates satellite cell-dependent myogenesis in response to resistance exercise through the inflammation pathway in human. Faseb J .2020; 34(1):1885-900.
  22. Tierney MT, Aydogdu T, Sala D, Malecova B, Gatto S, Puri PL, Latella L, Sacco A. STAT3 signaling controls satellite cell expansion and skeletal muscle repair. Nat Med. 2014; 20(10):1182-6.
  23. Ryen SvDd T, Francaux M, Deldicque L. Regulation of satellite cells by exercise in hypoxic conditions: a narrative review. European Journal of Applied Physiology. 2021; 121(Suppl 1).
  24. Joseph AM, Joanisse DR, Baillot RG, Hood DA. Mitochondrial dysregulation in the pathogenesis of diabetes: Potential for mitochondrial biogenesis-mediated interventions. Exp. Diabetes Res. 2012; 2012: 642038.
  25. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Dela F. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia. 2007; 50: 790–6.
  26. Van Thienen R, Masschelein E, D'Hulst G, Thomis M and Hespel P. Twin resemblance in muscle HIF-1α responses to hypoxia and exercise. Front Physiol. 2017; 7:676.
  27. Pircher T, Wackerhage H, Aszodi A, Kammerlander C, Böcker W and Saller MM. Hypoxic signaling in skeletal muscle maintenance and regeneration: a systematic review. Physiol. 2021; 12:684899.