Document Type : Original Article
Authors
1 PhD Student of Exercise Physiology, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Guilan, Guilan, Iran.
2 Full Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Guilan, Guilan, Iran.
Abstract
Background and Aim: It is well recognized that mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) are the key regulators of mitochondrial biogenesis and oxidative phosphorylation. This study investigated whether 12 weeks of interval training with high (HIIT) and moderate (MIIT) intensity influences the key regulatory molecules of mitochondrial biogenesis (TFAM and NRF-1( of skeletal muscle in type 2 diabetic male rats. Materials and Methods: Forty male rats (age: 8 weeks, weight: 180±20 g) were divided into two groups: high fat diet (HFD) including 32 rats, and standard diet (C) including 8 rats. After inducing type 2 diabetes via Streptozotocin, 8 diabetic rats (D) and 8 rats in group C were sacrificed and the remaining 24 rats were randomly assigned to three groups including diabetic control (DC), MIIT, and HIIT. The MIIT protocol includes 13 bouts of 4-minute activity with an equivalent intensity of 60-65% VO2max and the HIIT protocol includes 10 bouts of 4-minute activity with the equivalent intensity of 85-90% VO2max with 2 minute active rest periods that was performed for 12 weeks, and 5 sessions per week. Western blotting was used to measure the levels of TFAM and NRF1 proteins; and the parametric and non-parametric tests were used to analyze the data at the p≤0.05 level. Results: The results showed that TFAM and RNF-1 protein levels were significantly decreased in the D group compared to the C group (p<0.01). Indeed, exercise training resulted in an insignificant increase in protein levels of NRF-1 compared to the DC group (p>0.05); while HIIT and MIIT had no significant effect on protein levels of TFAM (p>0.05). Conclusion: It seems that the HIIT and MIIT programs improve mitochondrial respiration but have no effect on mitochondrial biogenesis in type 2 diabetic rats. However, further research is needed for definite results.
Keywords
Bishop, D.J., Botella, J., Genders, A.J., Lee, M.J., Saner, N.J., Kuang, J., ... & Granata, C. (2019). High-intensity exercise and mitochondrial biogenesis: current controversies and future research directions. Physiology, 34(1), 56-70.
Burgomaster, K.A., Howarth, K.R., Phillips, S.M., Rakobowchuk, M., MacDonald, M.J., McGee, S.L., & Gibala, M.J. (2008). Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. The Journal of Physiology, 586(1), 151-160.
Ding, H., Jiang, N., Liu, H., Liu, X., Liu, D., Zhao, F., ... & Zhang, Y. (2010). Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. Biochimica et Biophysica Acta (BBA)-General Subjects, 1800(3), 250-256.
Eckardt, K., Görgens, S.W., Raschke, S., & Eckel, J. (2014). Myokines in insulin resistance and type 2 diabetes. Diabetologia, 57(6), 1087-1099.
Flegal, K.M., Carroll, M.D., Ogden, C.L., & Curtin, L.R. (2010). Prevalence and trends in obesity among US adults, 1999-2008. Jama, 303(3), 235-241.
Friedman, R.L., Manly, S.P., McMahon, M., Kerr, I.M., & Stark, G.R. (1984). Transcriptional and post-transcriptional regulation of interferon-induced gene expression in human cells. Cell, 38(3), 745-755.
Frøsig, C., Rose, A.J., Treebak, J.T., Kiens, B., Richter, E.A., & Wojtaszewski, J.F. (2007). Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. Diabetes, 56(8), 2093-2102.
Gibala, M.J., Little, J.P., Van Essen, M., Wilkin, G.P., Burgomaster, K.A., Safdar, A., ... & Tarnopolsky, M.A. (2006). Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. The Journal of Physiology, 575(3), 901-911.
Gleyzer, N., Vercauteren, K., & Scarpulla, R.C. (2005). Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Molecular and Cellular Biology, 25(4), 1354-1366.
Goodyear, L.J., & Kahn, B.B. (1998). Exercise, glucose transport, and insulin sensitivity. Annual Review of Medicine, 49(1), 235-261.
Granata, C., Oliveira, R.S., Little, J.P., Renner, K., & Bishop, D.J. (2016). Training intensity modulates changes in PGC‐1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. The FASEB Journal, 30(2), 959-970.
Hafstad, A.D., Boardman, N.T., Lund, J., Hagve, M., Khalid, A.M., Wisløff, U., ... & Aasum, E. (2011). High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart. Journal of Applied Physiology, 111(5), 1235-1241.
Hafstad, A.D., Lund, J., Hadler-Olsen, E., Höper, A.C., Larsen, T.S., & Aasum, E. (2013). High-and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes, 62(7), 2287-2294.
Hey-Mogensen, M., Højlund, K., Vind, B. F., Wang, L., Dela, F., Beck-Nielsen, H., ... & Sahlin, K. (2010). Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes. Diabetologia, 53(9), 1976-1985.
Hock, M. B., & Kralli, A. (2009). Transcriptional control of mitochondrial biogenesis and function. Annual Review of Physiology, 71, 177-203.
Holloszy, J.O. (2009). Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. The American Journal of Clinical Nutrition, 89(1), 463S-466S.
Holmes, A., Coppey, L.J., Davidson, E.P., & Yorek, M.A. (2015). Rat models of diet-induced obesity and high fat/low dose streptozotocin type 2 diabetes: effect of reversal of high fat diet compared to treatment with enalapril or menhaden oil on glucose utilization and neuropathic endpoints. Journal of Diabetes Research, 2015.
Hotamisligil, G.S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860-867.
Jacobs, R.A., & Lundby, C. (2013). Mitochondria express enhanced quality as well as quantity in association with aerobic fitness across recreationally active individuals up to elite athletes. Journal of Applied Physiology, 114(3), 344-350.
Kaikini, A.A., Kanchan, D.M., Nerurkar, U.N., & Sathaye, S. (2017). Targeting mitochondrial dysfunction for the treatment of diabetic complications: pharmacological interventions through natural products. Pharmacognosy Reviews, 11(22), 128.
Khalafi, M., Mohebbi, H., Symonds, M.E., Karimi, P., Akbari, A., Tabari, E., ... & Moghaddami, K. (2020). The impact of moderate-intensity continuous or high-intensity interval training on adipogenesis and browning of subcutaneous adipose tissue in obese male rats. Nutrients, 12(4), 925.
Khalafi, M., Mohebbi, H., Karimi, P., Faridnia, M., & Tabari, E. (2018). The Effect of High Intensity Interval training and Moderate Intensity Continuous Training on Mitochondrial Content and PGC-1α of Subcutaneous Adipose Tissue in Male Rats with High Fat Diet Induced Obesity. Journal of Sport Biosciences, 10(3), 297-315. [Persian]
Liang, H., & Ward, W. F. (2006). PGC-1α: a key regulator of energy metabolism. Advances in Physiology Education.30 (4), 145-151
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.
Little, J.P., Safdar, A., Bishop, D., Tarnopolsky, M.A., & Gibala, M.J. (2011). An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 300, 1303-1310.
Lin, J., Handschin, C., & Spiegelman, B.M. (2005). Metabolic control through the PGC-1 family of transcription coactivators. Cell Metabolism, 1(6), 361-370.
Lowell, B.B., & Shulman, G.I. (2005). Mitochondrial dysfunction and type 2 diabetes. Science, 307(5708), 384-387.
Mendham, A.E., Duffield, R., Coutts, A.J., Marino, F., Boyko, A., & Bishop, D.J. (2015). Rugby-specific small-sided games training is an effective alternative to stationary cycling at reducing clinical risk factors associated with the development of type 2 diabetes: a randomized, controlled trial. PloS One, 10(6), e0127548.
Montero, D., Cathomen, A., Jacobs, R.A., Flück, D., de Leur, J., Keiser, S., ... & Lundby, C. (2015). Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. The Journal of Physiology, 593(20), 4677-4688.
Mootha, V.K., Lindgren, C.M., Eriksson, K.F., Subramanian, A., Sihag, S., Lehar, J., ... & Groop, L.C. (2003). PGC-1α responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genetics, 34(3), 267-273.
Morrison, D., Hughes, J., Della Gatta, P.A., Mason, S., Lamon, S., Russell, A.P., & Wadley, G.D. (2015). Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Free Radical Biology and Medicine, 89, 852-862.
Noakes, T., & Spedding, M. (2012). Run for your life. Nature, 487(7407), 295-296.
Perry, C.G., Lally, J., Holloway, G.P., Heigenhauser, G.J., Bonen, A., & Spriet, L.L. (2010). Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. The Journal of Physiology, 588(23), 4795-4810.
Petersen, K.F., Dufour, S., & Shulman, G.I. (2005). Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents. PLoS Medicine, 2(9), e233.
Ritov, V.B., Menshikova, E.V., Azuma, K., Wood, R., Toledo, F.G., Goodpaster, B.H., ... & Kelley, D.E. (2010). Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. American Journal of Physiology-Endocrinology and Metabolism, 298(1), E49-E58.
Scarpulla, R.C. (2002). Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene, 286(1), 81-89.
Scarpulla, R.C. (2008). Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Annals of the New York Academy of Sciences, 1147, 321.
Scarpulla, R. C. (2002). Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene, 286(1), 81-89.
Sriwijitkamol, A., Coletta, D.K., Wajcberg, E., Balbontin, G.B., Reyna, S.M., Barrientes, J., ... & Musi, N. (2007). Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study. Diabetes, 56(3), 836-848.
Steiner, J.L., Murphy, E.A., McClellan, J.L., Carmichael, M.D., & Davis, J.M. (2011). Exercise training increases mitochondrial biogenesis in the brain. Journal of Applied Physiology, 111(4), 1066-1071.
Tabari, E., Mohebbi, H., Karimi, P., Moghaddami, K., & Khalafi, M. (2019). The Effects of Interval Training Intensity on Skeletal Muscle PGC-1α in Type 2 Diabetic Male Rats. Iranian Journal of Diabetes and Metabolism, 18(4), 179-188. [Persian]
Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008). Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovascular Research, 79(2), 208-217.
Virbasius, J. V., Virbasius, C. M.A., & Scarpulla, R.C. (1993). Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Genes & Development, 7(3), 380-392.
)