The long-term effect of moderate-intensity exercise on the expression of the genes irisin and sirtuin-1 in the skeletal muscle of diabetic rats with streptozotocin

Document Type : Original Article

Authors

1 Department of Exercise Physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

2 Assistant Professor of Exercise Physiology, Department of Exercise Physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

Abstract

Disorders of glucose metabolism in various tissues, including skeletal muscle tissue and adipose tissue are features of diabetes. The aim of the present study was to evaluate the long-term effect of moderate-intensity continuous exercise on the expression of irisin and sirtuin-1 genes in the skeletal muscle of streptozotocin-nicotinamide-diabetic rats. Thirty-six 8-week-old males were randomly divided into three groups: healthy control (n = 12), diabetic (n = 12), and moderate-persistent diabetes (n = 12). Diabetic groups developed diabetes by intraperitoneal injection of nicotinamide and STZ solution at a doses of 95 and 55 mg/kg. The diabetic-moderate-intensity continuous exercise group performed their training protocol by running on a treadmill for 12 weeks, 5 sessions per week. Forty-eight hours after the last training session, the subjects were anesthetized and their horseshoe muscle tissue was removed and the expression of the genes Irisin and Sirtuin-1 was measured. 12 weeks of moderate-intensity continuous exercise in diabetic mice resulted in a significant increase in the expression of the genes Irisin and Sirtuin-1 (p <0.05). Performing 12 weeks of continuous exercise with moderate intensity in diabetic rats increased the expression of Irisin and sirtuin-1. Thus, changes in the expression of irisin and serotonin-1 may improve the symptoms of metabolic syndrome and can be a compensatory mechanism for reducing oxidative stress in diabetics.

What is already known on this subject?

It has been confirmed that irisin increases in circulation through regular exercise training and is involved in the conversion of white to brown adipose tissue.

 

What this study adds?

Twelve weeks of moderate-intensity aerobic exercise may improve the symptoms of metabolic syndrome, and changes in the expression of irisin and sirtuin-1 may also be a compensatory mechanism for reducing oxidative stress in diabetics.

Keywords

Main Subjects


Agh, F., Honarvar, N. M., Djalali, M., Nematipour, E., Gholamhoseini, S., Zarei, M., . . . Javanbakht, M. H. (2017). Omega-3 fatty acid could increase one of myokines in male patients with coronary artery disease: A randomized, double-blind, placebo-controlled trial. Archives of Iranian Medicine, 20(1), 1-10. URL: http://aimjournal.ir/Article/1116
Alipour, M., Salehi, I., & Soufi, F. G. (2012). Effect of exercise on diabetes-induced oxidative stress in the rat hippocampus. Iranian Red Crescent Medical Journal, 14(4), 222. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385801/
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., . . . Long, J. Z. (2012). A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 481(7382), 463-468. doi: https://doi.org/10.1038/nature10777
Casuso, R. A., Martínez-Amat, A., Hita-Contreras, F., Camiletti-Moirón, D., Aranda, P., & Martínez-López, E. (2015). Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats. Nutrition Research, 35(7), 585-591. doi: https://doi.org/10.1016/j.nutres.2015.05.007
Choi, J. E., & Mostoslavsky, R. (2014). Sirtuins, metabolism, and DNA repair. Current Opinion in Genetics & Development, 26, 24-32.  doi: https://doi.org/10.1016/j.gde.2014.05.005
Choi, Y. K., Kim, M.-K., Bae, K. H., Seo, H.-A., Jeong, J. Y., Lee, W. K., . . . Park, K. G. (2013). Serum irisin levels in new-onset type 2 diabetes. Diabetes Research and Clinical Practice, 100(1), 96-101. doi: https://doi.org/10.1016/j.diabres.2013.01.007
Eaton, M., Granata, C., Barry, J., Safdar, A., Bishop, D., & Little, J. P. (2018). Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle. Journal of Sport and Health Science, 7(2), 191-196. doi: https://doi.org/10.1016/j.jshs.2017.01.003
Eizadi, M., Ravasi, A. A., Soori, R., Baesi, K., & Choubineh, S. (2017). Effect of three months aerobic training on TCF7L2 expression in pancreatic tissue in type 2 diabetes rats induced by streptozotocin-nicotinamide. KAUMS Journal (FEYZ), 21(1), 1-8. doi: https://feyz.kaums.ac.ir/article-1-3274-en.html
Gurd, B. J., Perry, C. G., Heigenhauser, G. J., Spriet, L. L., & Bonen, A. (2010). High-intensity interval training increases SIRT1 activity in human skeletal muscle. Applied Physiology, Nutrition, and Metabolism, 35(3), 350-357. doi: https://doi.org/10.1139/H10-030
Hoffman, J. (2014). Physiological aspects of sport training and performance. Human Kinetics.
Huh, J., Dincer, F., Mesfum, E., & Mantzoros, C. (2014). Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. International Journal of Obesity, 38(12), 1538-1544. doi: https://doi.org/10.1038/ijo.2014.42
Jayakrishnapillai, P., Nair, S. V., & Kamalasanan, K. (2017). Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes. Colloids and Surfaces B: Biointerfaces, 153, 123-131. doi: https://doi.org/10.1016/j.colsurfb.2017.02.017
Khodadadi, H., Rajabi, H., Seyyed Reza Attarzadeh, S. R., & Abbasian, S. (2014). The effect of high intensity interval training (HIIT) and pilates on levels of irisin and insulin resistance in overweight women. Iranian Journal of Endocrinology and Metabolism, 16(3), 190-196. URL: http://ijem.sbmu.ac.ir/article-1-1709-en.html
Little, J. P., Safdar, A., Wilkin, G. P., Tarnopolsky, M. A., & Gibala, M. J. (2010). A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. The Journal of Physiology, 588(6), 1011-1022. doi: https://doi.org/10.1113/jphysiol.2009.181743
Menzies, K. J., Singh, K., Saleem, A., & Hood, D. A. (2013). Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis. Journal of Biological Chemistry, 288(10), 6968-6979. doi: https://doi.org/10.1074/jbc.M112.431155
Nie, Y., Erion, D. M., Yuan, Z., Dietrich, M., Shulman, G. I., Horvath, T. L., & Gao, Q. (2009). STAT3 inhibition of gluconeogenesis is downregulated by SirT1. Nature Cell Biology, 11(4), 492-500. doi: https://doi.org/10.1038/ncb1857
Ogden, C. L., Carroll, M. D., Kit, B. K., & Flegal, K. M. (2014). Prevalence of childhood and adult obesity in the United States, 2011-2012. Jama, 311(8), 806-814. doi: https://doi.org/10.1001/jama.2014.732
Oliveira, N. R., Marques, S. O., Luciano, T. F., Pauli, J. R., Moura, L. P., Caperuto, E., . . . Streck, E. L. (2014). Treadmill training increases SIRT-1 and PGC-1α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner. Mediators of Inflammation, 2014. URL: https://www.hindawi.com/journals/mi/2014/987017/
Pekkala, S., Wiklund, P. K., Hulmi, J. J., Ahtiainen, J. P., Horttanainen, M., Pöllänen, E., . . . Nyman, K. (2013). Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? The Journal of Physiology, 591(21), 5393-5400. doi: https://doi.org/10.1113/jphysiol.2013.263707
Prenzler, N. K., Macke, C., Horn, R., Brabant, G., Pabst, R., Richter, M., & Nave, H. (2007). Obesity influences the food consumption and cytokine pattern in ghrelin-treated endotoxemic rats. Life Sciences, 81(1), 80-87. doi: https://doi.org/10.1016/j.lfs.2007.04.030
Rotondi, M., Magri, F., & Chiovato, L. (2011). Thyroid and obesity: Not a one-way interaction. The Journal of Clinical Endocrinology & Metabolism, 96(2), 344-346. doi: https://doi.org/10.1210/jc.2010-2515
Saremi, A., Sh, S., & Kavyani, A. (2016). The Effect of aerobic training on metabolic parameters and 1serumlevel of Sirtuin1 in women with type 2 diabetes. AMUJ, 19(114), 88-97. URL: http://jams.arakmu.ac.ir/article-1-4511-en.pdf
Satoh, A., Stein, L., & Imai, S. (2011). The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Histone Deacetylases: the Biology and Clinical Implication, 125-162. doi: https://doi.org/10.1007/978-3-642-21631-2_7
Shirkhani, S., Marandi, M., Kazeminasab, F., Ghaedi, K., Esfarajani, F., & Nasr-Esfahani, M. (2019). The Effect of endurance training and high-fat diet on the expression of Pgc1α and Ucp1 in subcutaneous adipose and brown tissues of C57BL/6 male mice. Journal of Applied Exercise Physiology, 15(29), 89-102. doi: https://doi.org/10.22080/JAEP.2019.14462.1776
Soltani, M., Fathei, M., & Ghahremani Moghaddam, M. (2018). The effect of eight weeks of water training on Sirt1, Pgc-1α and body fat percentage in obese men. Journal of Babol University of Medical Sciences, 20(9), 55-60. doi: http://jbums.org/article-1-7580-en.html
Sun, C., Zhang, F., Ge, X., Yan, T., Chen, X., Shi, X., & Zhai, Q. (2007). SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell metabolism, 6(4), 307-319. doi: https://doi.org/10.1016/j.cmet.2007.08.014
Taghian, F. (2018). The impact of intensity interval training and supplementation of green tea on serum levels of irisin, insulin resistance in obese women with type 2 diabetes women. Iranian Journal of Diabetes and Metabolism, 17(6), 307-316. doi: http://ijdld.tums.ac.ir/article-1-5706-en.html
Timmons, J. A., Baar, K., Davidsen, P. K., & Atherton, P. J. (2012). Is irisin a human exercise gene? Nature, 488(7413), E9-E10. doi: https://doi.org/10.1038/nature11364
Tsiloulis, T., & Watt, M. J. (2015). Exercise and the regulation of adipose tissue metabolism. Progress in Molecular Biology and Translational Science, 135, 175-201. doi: https://doi.org/10.1016/bs.pmbts.2015.06.016
Wu, J., Boström, P., Sparks, L. M., Ye, L., Choi, J. H., Giang, A. H., . . . Schaart, G. (2012). Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 150(2), 366-376. doi: https://doi.org/10.1016/j.cell.2012.05.016
Wu, M. V., Bikopoulos, G., Hung, S., & Ceddia, R. B. (2014). Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: Impact on whole-body energy expenditure. Journal of Biological Chemistry, 289(49), 34129-34140. URL: https://www.jbc.org/article/S0021-9258(20)47362-4/fulltext
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002). AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings of the National Academy of Sciences, 99(25), 15983-15987. doi: https://doi.org/10.1073/pnas.252625599