Effects of eight weeks of high-intensity interval training on the expression of Pink1 and Parkin proteins in the liver tissue of type 2 diabetic male rats

Document Type : Original Article

Authors

Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

Abstract

Background and Purpose: There is a close relationship between liver mitochondrial dysfunction and the development of obesity and insulin resistance. As observed in type 2 diabetes, in conditions of insulin resistance, a decrease in insulin sensitivity of liver cells, skeletal muscle and fat cells is observed. In recent decades, physical activity has become a key tool in controlling many diseases, including type 2 diabetes, and studies have shown that various training protocols are effective in reducing the epidemic and improvement of some metabolic functions of the liver. The purpose of this study was to evaluate the effect of eight weeks of high intensity interval training (HIIT) on Parkin and Pink1 proteins in the liver tissue of type 2 diabetic rats.
Materials and Methods: In an experimental design, 30 three-month-old adult male Wistar rats with a weight range of 250-300 g were randomly divided into three groups of 10 including healthy control (C: intraperitoneal injection of saline), Diabetic control (D: diabetic with high-fat diet combined with intraperitoneal injection of streptozotocin) and trained diabetic (D+T: diabetic with exercise) were divided. The training protocol encompassed running at an intensity of 85%-90% of the maximum speed in 6 to 12 two-minute intervals; 5 days a week for eight weeks. Fourty eight hours after the last training session and after 12 to 14 hours of fasting, all rats were anesthetized and operated by a trained specialist without pain. A method based on Western blotting was used to determine changes in the expression profile of Parkin and Pink1 proteins in the heart muscle tissue (left ventricle) of rats. The two-way analysis of variance and Bonferroni’s post-hoc test were used to analyze the data.
Results: Induction of diabetes (D) causes a 51% and 63% increase in Parkin and Pink1 proteins, respectively, although it is not statistically significant (P>0.05). In addition, exercise intervention caused a 45% and 38% decrease in Parkin and Pink1 in the trained diabetic group (D+T) compared to the diabetic group (D), but it was not significant (p≥0.05).
Conclusion: According to the results, it can be stated that eight weeks of HIIT is insufficient to observe a significant reduction of mitophagy in the liver tissue of diabetic rats. At the same time, based on the partial changes of the indices, HIIT might be a preventive measure against the abnormal increase of mitophagy as a result of type 2 diabetes. However, to making a definite conclusion about these indices and how they are affected by different conditions more researches are needed.
 

Keywords

Main Subjects

References

  1. Sadeghpour Firozabadi E, Abdi A, Abbassi Daloii A. Effect of Aerobic Training with Aqueous Allium sativum L on IL-17, IL-22 Expression and Insulin Resistance in Diabetic Rats. Journal of Sport and Exercise Physiology. 2023;16(1):1-11. [In Persian]
  2. Dethlefsen MM KC, Tøndering AS, Lassen SB, Ringholm S, Pilegaard H. Impact of liver PGC‐1α on exercise and exercise training‐ induced regulation of hepatic autophagy and mitophagy in mice on HFF. Physiol Rep. 2018;6(13):13731-32.
  3. Su Z, Yutong Nie, Xiufang Huang, Ying Zhu, Bing Feng, Lipeng Tang, Guangjuan Zheng. Mitophagy in hepatic insulin resistance: Therapeutic potential and concerns. Frontiers in pharmacology 2019;10:1193.
  4. Wu H WY, Li W, Chen H, Du L, Liu D, et al. Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome. Autophagy. 2019;4:1-17.
  5. Twig G O. The interplay between mitochondrial dynamics and mitophagy. Antioxidants & redox signaling. 2011;14(10):1939-51.
  6. Narendra D TA, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy The Journal of cell biology 2008;183(5):795-803.
  7. Moreira OC EB, Martínez-Florez S, De Paz JA, Cuevas MJ, González-Gallego J. Mitochondrial function and mitophagy in the elderly: effects of exercise. Oxid Med Cell Longev. 2017;2012798.
  8. Brinkmann C PA, Metten A, Schiffer T, Bloch W, Brixius K, Gehlert S. Influence of endurance training on skeletal muscle mitophagy regulatory proteins in type 2 diabetic men. Endocr Res 2017 42(4):325-30.
  9. Memme JM, Avigail T. Erlich, Geetika Phukan, and David A. . Exercise and mitochondrial health. The Journal of physiology. 2021;599(3):803-17.
  10. JM. G. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012;590(5):1077-84.
  11. Larsen S DJ, Søndergård SD, Søgaard D, Vigelsoe A, Dybboe R, et al. . The effect of high‐intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue Scandinavian journal of medicine & science in sports. 2015;25(1).
  12. Ahmadi M ABBN. The effect of training on mitochondrial mitophagy factors in obese male rats. Journal of Sport and Exercise Physiology. 2022;15(2):10-9. [In Persian]
  13. Axelrod CL FC, Mulya A, Kirwan JP. Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro-elongation phenotype. Acta Physiol 2019 225(4):13216.
  14. Arribat Y, Broskey NT, Greggio C, Boutant M, Conde Alonso S, Kulkarni SS, Lagarrigue S, Carnero EA, Besson C, Cantó C, Amati F. Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training. Acta Physiologica. 2019 Feb;225(2):e13179.
  15. Sasidharan SR JJ, Anandakumar S, Venkatesan V, Ariyattu Madhavan CN, Agarwal A. . An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. BioMed research international. 2013;1.
  16. Esmailee B AA ADA, Farzanegi P. The effect of aerobic exercise along with resveratrol supplementation on AMPK and MAFbx gene expression of myocardial diabetic rats. Journal of Birjand University of Medical Sciences. 2020;27(2):150-60. [In Persian]
  17. Leandro CG LA, Hirabara SM, Manhães-de-Castro R. A program of moderate physical training for Wistar rats based on maximal oxygen consumption. Journal of Strength and Conditioning Research. 2007;21(3):751-6.
  18. Brown MB, Neves E, Long G, Graber J, Gladish B, Wiseman A, Owens M, Fisher AJ, Presson RG, Petrache I, Kline J. High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017;312(2):197-210.
  19. Dethlefsen MM, Kristensen CM, Tøndering AS, Lassen SB, Ringholm S, Pilegaard H. Impact of liver PGC‐1α on exercise and exercise training‐induced regulation of hepatic autophagy and mitophagy in mice on HFF. Physiological reports. 2018 Jul;6(13):13731.
  20. Hadidi V DF, Nemati J, et al. The Effect of Hind Limb Immobilization on Expression of Some Genes Involved in the Regulation of Mitochondrial Processes in Soleus Muscle of Trained and Untrained Rats. J Arak Uni Med Sci. 2019;22(1):51-61. [In Persian]
  21. Kwon IJ, Y. Lee, Y. Endurance Exercise-Induced Autophagy /Mitophagy Coincides with a Reinforced Anabolic State and Increased Mitochondrial Turnover in the Cortex of Young Male Mouse Brain. Journal of Molecular Neuroscience. (2021).71(1):42-54.
  22. Greene AW GK, Aguileta MA, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012;13:378-85.
  23. Yamano K YR. PINK1 is degraded through the N-end rule pathway. Autophagy. 2013;9:1758--69.
  24. Aerts L CK, De Strooper B, et al. PINK1 kinase catalytic activity is regulated by phosphorylation on serines 228 and 402. J Biol Chem ; . 2015;290:2798-811.
  25. Matsuda N SS, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211-21.
  26. Koyano F OK, Kosako H, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510:162-6.
  27. kheirandish Pishkenari M FP, Moradi L. Effect of aerobic training and octopamine on the gene expression of LAMP2A, Parkin and concentration OF SOD in liver of male rats fed with repeated heated oil. RJMS. 2021;28(2):1-10. [In Persian]
  28. Ju JS JS, Park JY, Lee JY, Lee SC, Cho KJ, Jeong JM. Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition. J Physiol Sci. 2016;66(5):417-30.
  29. Chen CC EA, Crilly MJ, Hood DA. Parkin is required for exercise-induced mitophagy in muscle: impact of aging. American Journal of Physiology-Endocrinology and Metabolism. 2018;315(3):404-15.

 

Files

History

  • Receive Date: 14 June 2023
  • Revise Date: 25 August 2023
  • Accept Date: 03 September 2023
  • First Publish Date: 19 September 2023
  • Publish Date: 22 November 2023

Share

How to cite

Statistics