The effect of high-intensity interval training (HIIT) on the content of eIF2α, ATF4 and CHOP proteins in the left ventricle of obese diabetic rats

Document Type : Original Article

Authors

1 Department of Physical Education, Farhangian University, Tehran, Iran

2 Department of Sport Sciences, Apadana Institute of Higher Education, Shiraz, Iran

Abstract

Background and Objective: The prevalence of obesity and diabetes is an epidemic and poses risks to public health. Therefore, the aim of the present study was to determine the effect of HIIT on the content of eIF2α, ATF4 and CHOP proteins in the left ventricle of obese diabetic rats.
Materials and Methods: The present study was experimental-basic. Twelve 2-month-old male Sprague-Dawley rats weighing 180±20 g were purchased. To induce type 2 diabetes, nicotinamide and streptozotocin solutions were injected at doses of 110 and 60 mg/kg, respectively. Blood sugar between 126 and 260 mg/dl was considered an index of type 2 diabetes. Rats were divided into control and HIIT groups. The HIIT group trained for 8 weeks, 3 days a week, with 5 4-minute sessions at an intensity of 85-95% of maximum speed, followed by 3-minute active rest periods at an intensity of 50-60% of maximum speed. After 48 hours from the last training session, the rats were anesthetized and left ventricular tissue was removed and the desired proteins were measured by Western blotting. The Shapiro-Wilk test and independent t-test were used to examine the data, and a significance level of P < 0.05 was considered.
Results: After 8 weeks of HIIT, the content of eIF2α (P=0.001), ATF4 (P=0.001), and CHOP (P=0.001) proteins in the left ventricle of the heart showed a significant increase compared to the control group.
Conclusion: The effects of HIIT on eIF2B, ATF4, and CHOP proteins likely induce cellular adaptations that could be an effective treatment for obese diabetic rats through the interaction of these proteins

Keywords

Main Subjects

References

  1. La Sala L, Pontiroli AE. Prevention of diabetes and cardiovascular disease in obesity. International Journal of Molecular Sciences. 2020;21(21):8178.
  2. Ren J, Bi Y, Sowers JR, Hetz C, Zhang Y. Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases. Nature Reviews Cardiology. 2021;18(7):499-521.
  3. Zhou Y, Murugan DD, Khan H, Huang Y, Cheang WS. Roles and therapeutic implications of endoplasmic reticulum stress and oxidative stress in cardiovascular diseases. Antioxidants. 2021;10(8):1167.
  4. AL O, EX F, RIMENTAL P, ICAL BME, IEN S. Cellular Response to Endoplasmic Reticulum Stress: Focus on XBP, elF2, ATF4, and CHOP. Journal of Experimental and Basic Medical Sciences. 2023;4(2):122-33.
  5. Amen OM, Sarker SD, Ghildyal R, Arya A. Endoplasmic reticulum stress activates unfolded protein response signaling and mediates inflammation, obesity, and cardiac dysfunction: therapeutic and molecular approach. Frontiers in Pharmacology. 2019;10:977.
  6. De Franco E, Caswell R, Johnson MB, Wakeling MN, Zung A, Dũng VC, et al. De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early-onset diabetes and transient hepatic dysfunction. Diabetes. 2020;69(3):477-83.
  7. Weiss CS, Ochs MM, Hagenmueller M, Streit MR, Malekar P, Riffel JH, et al. DYRK2 negatively regulates cardiomyocyte growth by mediating repressor function of GSK-3β on eIF2Bε. PLoS One. 2013;8(9):e70848.
  8. Matsumoto H, Miyazaki S, Matsuyama S, Takeda M, Kawano M, Nakagawa H, et al. Selection of autophagy or apoptosis in cells exposed to ER-stress depends on ATF4 expression pattern with or without CHOP expression. Biology Open. 2013;2(10):1084-90.
  9. Wang X, Zhang G, Dasgupta S, Niewold EL, Li C, Li Q, et al. ATF4 protects the heart from failure by antagonizing oxidative stress. Circulation Research. 2022;131(1):91-105.
  10. Freundt JK, Frommeyer G, Wötzel F, Huge A, Hoffmeier A, Martens S, et al. The transcription factor ATF4 promotes expression of cell stress genes and cardiomyocyte death in a cellular model of atrial fibrillation. BioMed Research International. 2018;2018(1):3694362.
  11. Olivares-Silva F, Espitia-Corredor J, Letelier A, Vivar R, Parra-Flores P, Olmedo I, et al. TGF-β1 decreases CHOP expression and prevents cardiac fibroblast apoptosis induced by endoplasmic reticulum stress. Toxicology In Vitro. 2021;70:105041.
  12. Nam D-H, Han J-H, Lee T-J, Shishido T, Lim JH, Kim G-Y, et al. CHOP deficiency prevents methylglyoxal-induced myocyte apoptosis and cardiac dysfunction. Journal of Molecular and Cellular Cardiology. 2015;85:168-77.
  13. Liu Y. Hydrogen peroxide induces nucleus pulposus cell apoptosis by ATF4/CHOP signaling pathway. Experimental and Therapeutic Medicine. 2020;20(4):3244-52.
  14. Pahlavani HA, Khozani MN, Bahmanbeglouu NA, Zouhal H. Simultaneous effects of high-speed circuit training (HSCT) and high-speed interval training (HSIT) on physical fitness and lung volumes of males after coronavirus disease. Journal of Bodywork and Movement Therapies. 2024.
  15. Daryanoosh F, Moghadam MS, Pahlavani HA, Bahmanbeglou NA, Mirzaei S. The effect of high-intensity interval training (HIIT) on the expression of proteins involved in autophagy, apoptosis, and atrophy pathways in the myocardium of male rats with type 2 diabetes. 2022. DOI: https://doi.org/10.21203/rs.3.rs-2105962/v1.
  16. Sherafati-Moghadam M, Pahlavani HA, Daryanoosh F, Salesi M. The effect of high-intensity interval training (HIIT) on protein expression in Flexor Hallucis Longus (FHL) and soleus (SOL) in rats with type 2 diabetes. Journal of Diabetes & Metabolic Disorders. 2022;21(2):1499-508.
  17. Alizadeh Palavani H, Yaghmaei M, Mirzaee Moghamir S, Salboukhi R. The Effect of High-Intensity Interval Training on the Amount of BECLIN1/2 Family Autophagy Proteins in the Left Ventricle of the Heart in Rats with Type 1 Diabetes. Iranian Journal of Diabetes and Metabolism. 2023;23(4):236-44.
  18. Alizadeh Pahlavani H, Marezloo M, Aghaei Bahmanbeglou N, Asgharpour H. The effect of high-intensity interval training (HIIT) on the contents of dynamin-like protein 1 (DRP1) and optic atrophy 1 (OPA1) in the left ventricle of aged male rats. Journal of Isfahan Medical School. 2024.
  19. Pahlavani HA, Rajabi H, Nabiuni M, Motamedi P, Khaledi N. The effect of anaerobic exercise with melatonin consumption on the expression of Bax and Bcl-2 markers in rat myocardium after ischemic-reperfusion. Majallah-i pizishki-i Danishgah-i Ulum-i Pizishki va Khadamat-i Bihdashti-i Darmani-i Tabriz. 2019;41(3):68-77.
  20. Alizadeh Pahlavani H, Rajabi H, Nabiuni M, Motamedi P, Khaledi N. The effect of anaerobic exercise with melatonin consumption on the expression of Bax and Bcl-2 markers in rat myocardium after ischemic-reperfusion. Medical Journal of Tabriz University of Medical Sciences and Health Services. 2019;41(3):68-77.
  21. Jahani M, Matinhomaie H, Farzanegi P. Changes Of Perk And Chop Proteins In Endoplasmic Reticulum Of Cardiac Myocytes And Tnf In Diabetic Wistar Rats Following Continuous And Interval Exercise. Iranian Journal of Diabetes and Metabolism. 2020;19(4):195-204.
  22. Fathi R, Ebrahimi M, Khenar Sanami S. Effects of High Fat Diet and High Intensity Aerobic Training on Interleukin 6 Plasma Levels in Rats. Pathobiology Research. 2015;18(3):109-16.
  23. Safhi MM, Anwer T, Khan G, Siddiqui R, Sivakumar SM, Alam MF. The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats. The Korean Journal of Physiology & Pharmacology. 2018;22(5):493-501.
  24. Khalili A, Nekooeian AA, Khosravi MB. Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes. Journal of Asian Natural Products Research. 2017;19(10):1011-21.
  25. Garcia NF, Sponton AC, Delbin MA, Parente JM, Castro MM, Zanesco A, et al. Metabolic parameters and responsiveness of isolated iliac artery in LDLr-/-mice: role of aerobic exercise training. American Journal of Cardiovascular Disease. 2017;7(2):64.
  26. Khoramshahi S, Kordi M, Delfan M, Gaeini A, Safa M. Effect of five weeks of high-intensity interval training on the expression of miR-23a and Atrogin-1 in gastrocnemius muscles of diabetic male rats. Iranian Journal of Endocrinology and Metabolism. 2017;18(5).
  27. Alizadeh Pahlavani H, Laher I, Knechtle B, Zouhal H. Exercise and mitochondrial mechanisms in patients with sarcopenia. Frontiers in Physiology. 2022;13:1040381.
  28. Pahlavani HA. Exercise-induced signaling pathways to counteracting cardiac apoptotic processes. Frontiers in Cell and Developmental Biology. 2022;10:950927.
  29. Kim Y-A, So W-Y. Effects of a single bout of aerobic exercise on skeletal muscle protein turnover in mice. Journal of Men's Health. 2018;14(1):e6-e15.
  30. D'Hulst G, Masschelein E, De Bock K. Resistance exercise enhances long-term mTORC1 sensitivity to leucine. Molecular Metabolism. 2022;66:101615.
  31. Kim KH, Kim SH, Min Y-K, Yang H-M, Lee J-B, Lee M-S. Acute exercise induces FGF21 expression in mice and in healthy humans. PloS One. 2013;8(5):e63517.
  32. Zlobine I, Gopal K, Ussher JR. Lipotoxicity in obesity and diabetes-related cardiac dysfunction. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2016;1861(10):1555-68.
  33. Ghosh A, Shcherbik N. Effects of oxidative stress on protein translation: Implications for cardiovascular diseases. International Journal of Molecular Sciences. 2020;21(8):2661.
  34. Ghafouri-Fard S, Abak A, Khademi S, Shoorei H, Bahroudi Z, Taheri M, et al. Functional roles of non-coding RNAs in atrophy. Biomedicine & Pharmacotherapy. 2021;141:111820.
  35. Pelozin BR, Soci UP, Gomes JL, Oliveira EM, Fernandes T. mTOR signaling-related microRNAs as cardiac hypertrophy modulators in high-volume endurance training. Journal of Applied Physiology. 2022;132(1):126-39.
  36. Bourdier G, Flore P, Sanchez H, Pepin J-L, Belaidi E, Arnaud C. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size. American Journal of Physiology-Heart and Circulatory Physiology. 2016;310(2):H279-H89.
  37. Yuan Z, Xiao-Wei L, Juan W, Xiu-Juan L, Nian-Yun Z, Lei S. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. Journal of Physiology and Biochemistry. 2022;78(3):641-52.
  38. Pasini AMF, Stranieri C, Rigoni AM, De Marchi S, Peserico D, Mozzini C, et al. Physical exercise reduces cytotoxicity and up-regulates nrf2 and upr expression in circulating cells of peripheral artery disease patients: an hypoxic adaptation? Journal of Atherosclerosis and Thrombosis. 2018;25(9):808-20.
  39. Marafon BB, Pinto AP, Ropelle ER, de Moura LP, Cintra DE, Pauli JR, et al. Muscle endoplasmic reticulum stress in exercise. Acta Physiologica. 2022;235(1):e13799.
  40. Kim K, Kim Y-H, Lee S-H, Jeon M-J, Park S-Y, Doh K-O. Effect of exercise intensity on unfolded protein response in skeletal muscle of rat. The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology. 2014;18(3):211.
  41. Zolfaghari M, Faramarzi M, Hedayati M, Ghaffari M. The effect of resistance and endurance training with ursolic acid on atrophy‐related biomarkers in muscle tissue of diabetic male rats induced by streptozotocin and a high‐fat diet. Journal of Food Biochemistry. 2022;46(8):e14202.
  42. Bayat H, Gholami M, Rajabi H, Abed Natanzi H. The effect of high-intensity interval training on the expressions of CHOP and ATF6 in liver tissue in rats with type 2 diabetes. Journal of Applied Health Studies in Sport Physiology. 2024;11(1):96-110.
  43. Estébanez B, Moreira OC, Almar M, de Paz JA, Gonzalez-Gallego J, Cuevas MJ. Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects. European Journal of Sport Science. 2019;19(7):931-40.
Daneshvar Medicine
Volume 32, Issue 6 - Serial Number 175
March and April 2025
Pages 41-52

Files

Share

How to cite

Statistics