The effect of training on mitochondrial mitophagy factors in obese male rats

Document Type : original article

Authors

1 Department of Physical Education and Sport Sciences Yadegar-e- Imam Khomeini (RAH) Shahr-e Rey Branch, Islamic Azad University, Tehran, Iran

2 Faculty of Physical Education, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul Branch, Iran

Abstract

purpose: Mitophagy can assist in mitochondrial quality control. The aim of this study was to investigate the effect of training on mitochondrial mitophagy factors in obese male rats.
Methods: In this experimental study, 40 male rats (weight 120 ± 20 g) after inducing obesity with high fat diet (for 10 weeks), eight rats from the high-fat diet group (O) and eight rats of the standard dietary group (C) to investigate the induction of obesity were described and other obese rats were randomly divided into three groups: obesity control (OC), moderate intensity continuous training (MICT) and high intensity interval training (HIIT). The HIIT protocol includes 10 bouts of 4-minute activity with intensity of 85-90% vo2max and 2-minute active rest periods and MICT protocols performed five sessions per week, with intensity of 65-70% VO2max for 12 weeks. Bcl2 and parkin levels were measured by gel electrophoresis and western blotting. Data were analyzed by One-way ANOVA and post hoc Tukey at P ≤ 0.05.
Results: The results showed that both HIIT and MICT training significantly increased bcl2 and PARKIN of Soleus muscle in comparison with the control group (P < 0.05). However, there was no significant difference between the two groups of HIIT and MICT in bcl2 and PARKIN levels of Soleus muscle in obese male rats (P > 0.05).
Conclusion: According to the results, it seems that HIIT and MICT can help reduce mitochondrial degradation and impairment in skeletal muscle during obesity.

Keywords

References

  1. Schell LM and Gallo MV. Overweight and obesity among North American Indian infants, children, and youth. Am J Hum Biol. 2012;24:302–13.
  2. Collins KH, Herzog W, MacDonald GZ, Reimer RA, Rios JL, Smith IC, Zernicke RF, Hart DA. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity. Front Physiol. 2018;23;9:112.
  3. Mu Y, Yan WJ, Yin TL, Zhang Y, Li J, Yang J. Diet-induced obesity impairs spermatogenesis: A potential role for autophagy. Sci Rep. 2017;7:43475.
  4. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005;307:384–387.
  5. Szendroedi J, Phielix E, Roden, M. The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2011;8: 92–103.
  6. Liu L, Sakakibara K, Chen Q, Okamoto K. Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res. 2014;24: 787–795.
  7. Okamoto K. Organellophagy: eliminating cellular building blocks via selective autophagy. J. Cell Biol. 2014;205: 435–445.
  8. Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 2015;85:257–273.
  9. Pickles S, Vigié P, Youle RJ. Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance. Curr Biol. 2018; 28(4):R170-R185.
  10. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433-446.
  11. Campello S, Strappazzon F, Cecconi F. Mitochondrial dismissal in mammals, from protein degradation to mitophagy. Biochim Biophys Acta. 2014;1837:451-460
  12. Ni HM, Williams JA, Ding WX. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2015;4:6-13.
  13. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12:9–14.
  14. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119–131.
  15. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 2010;107: 378–383
  16. Hollville E, Carroll RG, Cullen SP, Martin SJ. Bcl-2 family proteins participate in mitochondrial quality control by regulating Parkin/PINK1-dependent mitophagy. Mol Cell. 2014;55(3):451-66.
  17. Hardwick JM, Soane L. Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol. 2013;5(2)31-44
  18. Decuypere JP, Parys JB, Bultynck G. Regulation of the autophagic bcl-2/beclin 1 interaction. Cells. 2012;1(3):284-312.
  19. Autret A, Martin SJ. Bcl-2 family proteins and mitochondrial fission/fusion dynamics. Cell. Mol. Life Sci. 2010;67, 1599-1606
  20. Yan Z, Lira VA, Greene NP. Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev. 2012;40:159-164.
  21. Ding H, Jiang N, Liu H, Liu X, Liu D, Zhao F, et al. Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. Biochim Biophys Acta. 2010; 1800:250-256.
  22. Türk Y, Theel W, Kasteleyn MJ, F Franssen ME, Hiemstra PS, Rudolphus AC. Taube, Braunstahl GJ. High intensity training in obesity: A Meta‐analysis Obes Sci Pract. 2017; 3(3): 258–271.
  23. Levine, B., Packer, M., and Codogno, P. Development of autophagy inducers in clinical medicine. J. Clin. Invest. 2015;125: 14–24.
  24. Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N. Engl. J. Med. 2013;368: 651–662.
  25. Kubli DA, Gustafsson AB. Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 2012;111: 1208–1221
  26. Greene NP, Lee DE, Brown JL, Rosa ME, Brown LA, Perry RA, et al. Mitochondrial quality control, promoted by PGC-1α, is dysregulated by Western diet-induced obesity and partially restored by moderate physical activity in mice. Physiol Rep. 2015;3: e12470.
  27. Axelrod CL, Fealy CE, Mulya A, Kirwan JP. Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro-elongation phenotype. Acta Physiol (Oxf). 2019 Apr;225(4):e13216.
  28. Ju JS, Jeon SI, Park JY, Lee JY, Lee SC, Cho KJ, et al. Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition. J. Physiol. Sci. 2016;6:417–430.
  29. Siahkohian M, Asgharpour-arshad M, Bolboli L, Jafari A, Sheikhzadeh hesari F. Effect of 12- Weeks Aerobic Training on Some Indices of Skeletal Muscle Apoptosis in Male Rats. Med J Tabriz Uni Med Sciences Health Services 2018; 39(6):35-43.
  30. Stewart CE, Rittweger J. Adaptive processes in skeletal muscle: Molecular regulators and genetic influences. J Musculoskelet Neuronal Interact 2006;6(1):73-86.
  31. Dilger AC, Spurlock ME, Grant AL, Gerrard DE. Myostatin null mice respond differently to dietary-induced and genetic obesity. Anim Sci J. 2010;81(5):586-93
  32. Evans CC, LePard KJ, Kwak JW, Stancukas MC, Laskowski S, Dougherty J, et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PloS one. 2014;9(3):e92193.
  33. Hafstad AD, Lund J, Hadler-Olsen E, Höper AC, Larsen TS, Aasum E. High-and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes. 2013;62(7):2287-94
  34. Vainshtein A, Tryon LD, Pauly M, Hood DA. Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am. J. Physiol. Cell Physiol. 2015;308:C710–9.
  35. Tarpey MD, Davy KP, McMillan RP, Bowser SM, Halliday TM, Boutagy NE, et al. Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal. Mol Metab. 2017;6(12):1597-1609.
  36. Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training-induced increase in autophagy markers in human skeletal muscle. Physiol Rep. 2018;6(7):e13651.
  37. Brandt, N., L. Nielsen, B. Thiellesen Buch, A. Gudiksen, S. Ringholm, Y. Hellsten, et al. Impact of b-adrenergic signaling in PGC-1a-mediated adaptations in mouse skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2017;314: 1–20.
  38. Hood DA. Invited review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol. 2001;90:1137–57
  39. Drake JC, Wilson RJ, Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB J. 2016;30:13–22.
  40. Fu T, Xu Z, Liu L, Guo Q, Wu H, Liang X, et al. Mitophagy Directs Muscle-Adipose Crosstalk to Alleviate Dietary Obesity. Cell Rep. 2018;23(5):1357-1372.
  41. Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 2013;17:162–184.
  42. Jin SM, Youle RJ. The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediatedmitophagy of polarized mitochondria. Autophagy. 2013;9(11):1750-7.
  43. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. The Journal of pathology. 2010;221(1):3-12
  44. Ploumi C, Daskalaki I, Tavernarakis N. Mitochondrial biogenesis and clearance: a balancing act. The FEBS journal. 2017;284(2):183-95
  45. Maulik N, Sasaki H, Addya S, Das DK. Regulation of cardiomyocyte apoptosis by redox-sensitive transcription factors. FEBS Lett 2000;485:7-12.
  46. Liu WY, He W, Li H. Exhaustive training increases uncoupling protein 2 expression and decreases Bcl-2/Bax ratio in rat skeletal muscle. Oxid Med Cell Longev. 2013;12:1-7

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History

  • Receive Date: 08 April 2019
  • Revise Date: 23 April 2020
  • Accept Date: 19 May 2020
  • First Publish Date: 21 November 2021
  • Publish Date: 21 April 2022

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