Effect of high intensity interval training on adipose tissue levels of steroid receptor RNA activator and insulin resistance index in rats with type II diabetes

Document Type : Original Article


Department of physical education, Bojnourd branch, Islamic Azad University, Bojnourd, Iran


Background and Purpose: Steroid receptor RNA activator (SRA) is one of the long non-coding RNA (LncRNA) playing a dual role in glucose homeostasis and insulin resistance. Purpose of this study was to investigate the effect of six weeks of high intensity interval training on adipose tissue levels of SRA and insulin resistance index in diabetic rats with high fat diet and streptozotocin.  Materials and Methods: Twenty male wistar rats (10-12 weeks old; 200-300 gr) were selected and type 2 diabetes was induced by six weeks of high-fat diet and streptozotocin injection. Afterwards, obese diabetic rats were randomly divided into experimental and control groups. The rats in the experimental group participated in six weeks of high intensity interval training included 40 seconds of running on a treadmill at 25-35 m/min followed by 2 minutes of active rest at 10 m/min, which was performed for 30 minutes per session, five sessions per week, 6 weeks. All rats were dissected 48 hours after the last training session and adipose levels of SRA, serum levels of insulin and fasting blood sugar were evaluated using appropriate laboratory methods. Data analyses were carried out using independent and paired t-test and Pearson's correlation test at a significance level of less than 0.05. Results: Six weeks of high intensity interval training resulted in significant decreases in adipose tissue levels of Steroid Receptor RNA Activator (P=0.001) in addition to significant decreases in levels of insulin (P<0.001), fasting blood glucose (P<0.001), insulin resistance index (P<0.001) and body weight (P=0.028) in the experimental group compared to the control group. Furthermore, six weeks of high intensity interval training in experimental group caused significant decreases in body weight in post- test compared to pre- test (P<0.001). However, according to the Pearson’s correlation test, there were no significant correlations between the changes in steroid receptor RNA activator levels of adipose tissue and changes in other variables following high intensity interval training (P>0.05) Conclusion: It seems that in addition to improving body composition, six weeks of high intensity interval training play a role in improving insulin resistance through decreasing the levels of SRA.


Main Subjects

  1. Bonnefond A, Froguel P. Rare and common genetic events in type 2 diabetes: what should biologists know? Cell Metab. 2015; 21:357–368.
  2. Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, Vazquez J, Valencia A, Tress ML. Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Hum Mol Genet. 2014; 23: 5866–5878.
  3. Hangauer MJ, Vaughn IW, McManus MT. Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 2013; 9:e1003569.
  4. Harries LW. Long non-coding RNAs and human disease. Biochem Soc Trans. 2012; 40 (4): 902–906.
  5. Kumar V, Westra HJ, Karjalainen J, Zhernakova DV, Esko T, Hrdlickova B, Almeida R, Zhernakova A, Reinmaa E, Vosa U, Hofker MH, Fehrmann RS, Fu J, Withoff S, Metspalu A, Franke L, Wijmenga C. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet. 2013; 9:e1003201.
  6. Chen G, Qiu C, Zhang Q, Liu B, Cui Q. Genome-wide analysis of human SNPs at long intergenic noncoding RNAs. Hum Mutat. 2013; 34:338–344. 
  7. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, O’Malley BW. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. 1999; 97:17–27.
  8. Lanz RB, Razani B, Goldberg AD, O’Malley BW. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) Proc Natl Acad Sci U S A. 2002; 99:16081–16086.
  9. Hubé F, Velasco G, Rollin J, Furling D, Francastel C. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Nucleic Acids Research. 2011; 39, 513–525.
  10. Xu B, Yang WH, Gerin I, Hu CD, Hammer GD, Koenig RJ. Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis. Mol Cell Biol. 2009; 29(7):1719-34.
  11. Friedrichs F, Zugck C, Rauch Gj, Ivandic B, Weichenhan D, Müller-Bardorff M, Meder B, Mokhtari NE, Regitz-Zagrosek V, Hetzer R, Schäfer A, Schreiber S, Chen J, Neuhaus I, Ji R, Siemers NO, Frey N, Rottbauer W, Katus HA, Stoll M. HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy. Genome Res. 2009; 19(3): 395–403.
  12. Chen G, Yu D, Nian X, Liu J, Koenig R, Xu B, Sheng L. LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL). Sci Rep. 2016; 6:35531.
  13. Xu B, Gerin I, Miao H, Vu-Phan D, Johnson CN, Xu R, Chen XW, Cawthorn WP, MacDougald OA, Koenig RJ. Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity. PLoS One. 2010; 5:e14199.
  14. Liu S, Xu R, Gerin I, Cawthorn WP, Macdougald OA, Chen XW, Saltiel AR, Koenig RJ, Xu B. SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and downstream signaling. PLoS One. 2014; 9:e95416.
  15. Liu S, Sheng L, Miao H, Saunders TL, MacDougald OA, Koenig RJ, Xu B. SRA gene knockout protects against diet-induced obesity and improves glucose tolerance. J Biol Chem. 2014; 289:13000–13009.
  16. Yang S, Sun J. LncRNA SRA deregulation contributes to the development of atherosclerosis by causing dysfunction of endothelial cells through repressing the expression of adipose triglyceride lipase. Mol Med Rep. 2018; 18:5207-5214.
  17. Wu B, Ding J, Chen A, Song Y, Xu C, Tian F, Zhao J. Aerobic exercise improves adipogenesis in diet-induced obese mice via the lncSRA/p38/JNK/PPARγ pathway. Nutrition Research. 2022a; 105: 20-32
  18. Wu B, Xu C, Tian Y, Zeng Y, Yan F, Chen A, Zhao J, Chen L. Aerobic exercise promotes the expression of ATGL and attenuates inflammation to improve hepatic steatosis via lncRNA SRA. Scientific Reports. 2022b; 12: 5370.
  19. Abedi B, Okhovat E. The Effect of 8 Weeks of High-Intensity Interval Training (HIIT) on Serum Adiponectin Levels and Insulin Resistance of Women with Type 2 Diabetes. Journal of Sport Biosciences. 2016; 8(3): 411-426. [In Persian]
  20. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White RD. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes care. 2006; 29(6):1433-8.
  21. Alamdar S, Avendi SM. The Effect of high intensity interval training with nigella sativa supplementation on lipid profile, fasting blood sugar and body composition of overweight young women. Journal of Sport and Exercise Physiology. 2023; 16(1): 35-45. [In Persian]
  22. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. J Physiol. 2012; 590(5):1077-84.
  23. Sun YP, Lu NC, Parmley WW, Hollenbeck CB. Effect of cholesterol diets on vascular function and Atherogenesis in rabbits. Proc Soc Exp Bio Med; 2000.224(3): 166-71.
  24. Eizadi M, Ravasi AA, Soory R, Baesi K, Choobineh S. The Effect of Three Months of Resistance Training on TCF7L2 Expression in Pancreas Tissues of Type 2 Diabetic Rats. Avicenna Journal of Medical Biochemistry. 4(1):e34014.
  25. Reilly SM, Saltiel AR. Adapting to obesity with adipose tissue inflammation. Nature Reviews Endocrinology. 13:633–43.
  26. Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology and Prevention and Cardiac Rehabilitation and Exercise Physiology. 2007. 14(6), 753–760.
  27. Kalhor H, Peeri M, Matin Homaee H, Izadi M. The Effect of 6 Weeks Resistance Training and HITT on GLP-1 Gene Expression of Diabetic Rats. Iranian Journal of Diabetes and Obesity. 2018. 10(1): 42-9. [In Persian]
  28. Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS, Grunberger G. α2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Molecular and Cellular Endocrinology. 2000. 164(1-2), 87-98.
  29. Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011; 12: 722–734.
  30. Siersbaek R, Nielsen R, Mandrup S. Transcriptional networks and chromatin remodeling controlling adipogenesis. Trends Endocrinol Metab. 2012; 23: 56–64.
  31. Aouadi M, Binetruy B, Caron L, Le Marchand-Brustel Y, Bost F. Role of MAPKs in development and differentiation: lessons from knockout mice. Biochimie. 2006; 88:1091–1098.
  32. Kochumon S, Arefanian H, Sindhu S, Shenouda S, Thomas R, Al-Mulla F, Tuomilehto J, Ahmad R. Adipose tissue steroid receptor rna activator 1 (sra1) expression is associated with obesity, insulin resistance, and inflammation. Cells. 2021; 10: 2602.
  33. Kochumon SH, Arefanian H, Sindhu S, Thomas R, Jacob T, Al-Sayyar A, Shenouda S, Al-Rashed F, Koistinen HA, Al-Mulla F, Tuomilehto J, Ahmad R. Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity. Cells. 2022; 11(24): 4007.
  34. Daloii Abbassi A, Abdi A, Firozabadi Sadeghpour E. 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. 16(1):1-11. [In Persian]


  • Receive Date: 17 July 2023
  • Revise Date: 25 October 2023
  • Accept Date: 02 November 2023
  • First Publish Date: 22 November 2023
  • Publish Date: 21 January 2024