Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 PhD student of Exercise Physiology, Faculty of Physical Education andSport Sciences, TehranUniversity, Tehran, Iran

2 Professor, Department of ExercisePhysiology, Faculty of Physical Education and Sport Sciences, Central Tehran Branch, Islamic Azad University, Tehran(Sohanak), Iran

3 . Assistant Professor, Department of ExercisePhysiology, Faculty of Physical Education and Sport Sciences,Alzahra University, Tehran, Iran


The aim of this study was to compare the effect of high intensity interval training (HIIT) and continuous endurance training (E) on gene expression of adiponectin and TNF-α in type 2 diabetic rats. 24 Wistar rats (weight 160 ± 10 g) were divided into three groups: control, high intensity interval training and continuous endurance training after 7 months of high-fat diet containing fructose. The training groups performed the training protocol for 8 weeks / 5 days a week. The gene expression of adiponectin and TNF-α were measured from visceral fat tissue and glucose and insulin were measured from plasma and insulin resistance index was calculated. Data were analyzed by ANOVA and Pearson correlation. Both types of training significantly increased the expression of adiponectin (P=0.016), but there was no significant difference between the two training groups (P=0.932). The gene expression of TNF-α decreased in training groups and this decrease was more prominent in the HIIT group (P=0.001). There was a significant relationship between reduction of insulin resistance and reduction of TNF-α gene expression (P<0.001, r=0.09) and increase of adiponectin gene expression (P=0.002, r= -0.7). HIIT may have an effective role in the balance between anti-inflammatory and inflammatory factors and regulation of insulin resistance in rats with type 2 diabetes.


1.   Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840-6.
2.   DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015;1:15019.
3.   Abdullah A, Stoelwinder J, Shortreed S, Wolfe R, Stevenson C, Walls H, et al. The duration of obesity and the risk of type 2 diabetes. Public health nutrition. 2011;14(1):119-26.
4.   Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology. 2011;11(2):98-107.
5.   Wang X, Bao W, Liu J, Ouyang YY, Wang D, Rong S, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36(1):166-75.
6.   Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302(2):179-88.
7.   Ghareghani P, Shanaki M, Ahmadi S, Khoshdel AR, Rezvan N, Meshkani R, et al. Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice. Obesity Research & Clinical Practice. 2017.
8.   Moller DE. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab. 2000;11(6):212-7.
9.   Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001;286(10):1218-27.
10. Henriksen EJ. Invited review: Effects of acute exercise and exercise training on insulin resistance. J Appl Physiol (1985). 2002;93(2):788-96.
11. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol (1985). 2004;96(1):101-6.
12. Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33(12):e147-67.
13. 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.
14. Khoramshahi S, Kordi MR, Delfan M, Gaeini AA, 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):361-7.
15. Fukushima M, Hattori Y, Tsukada H, Koga K, Kajiwara E, Kawano K, et al. Adiponectin gene therapy of streptozotocin‐induced diabetic mice using hydrodynamic injection. The journal of gene medicine. 2007;9(11):976-85.
17. Alizadeh M, Asad MR, Faramarzi M, Afroundeh R. Effect of Eight-Week High Intensity Interval Training on Omentin-1 Gene Expression and Insulin-Resistance in Diabetic Male Rats. Annals of Applied Sport Science. 2017;5(2):29-36.
18. Gillen JB, Little JP, Punthakee Z, Tarnopolsky MA, Riddell MC, Gibala MJ. Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(6):575-7.
19. Leandro CG, Levada AC, 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.
20. Ahmadizad S, Haghighi AH, Hamedinia MR. Effects of resistance versus endurance training on serum adiponectin and insulin resistance index. European Journal of Endocrinology. 2007;157(5):625-31.
21. Festa A, D’Agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000;102(1):42-7.
22. Plaisance EP, Grandjean PW. Physical activity and high-sensitivity C-reactive protein. Sports Medicine. 2006;36(5):443-58.
23. Keller C, Keller P, Giralt M, Hidalgo J, Pedersen BK. Exercise normalises overexpression of TNF-α in knockout mice. Biochemical and biophysical research communications. 2004;321(1):179-82.
24. van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF. Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. Journal of Clinical Investigation. 1996;97(3):713.
25. Vieira VJ, Valentine RJ, Wilund KR, Antao N, Baynard T, Woods JA. Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice. American Journal of Physiology-Endocrinology and Metabolism. 2009;296(5):E1164-E71.
26. Sakurai T, Izawa T, Kizaki T, Ogasawara J-e, Shirato K, Imaizumi K, et al. Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. Biochemical and biophysical research communications. 2009;379(2):605-9.
27. Pervaiz N, Hoffman-Goetz L. Immune cell inflammatory cytokine responses differ between central and systemic compartments in response to acute exercise in mice. Exerc Immunol Rev. 2012;18:142-57.
28. Martín-Cordero L, García JJ, Hinchado MD, Bote E, Manso R, Ortega E. Habitual physical exercise improves macrophage IL-6 and TNF-α deregulated release in the obese zucker rat model of the metabolic syndrome. Neuroimmunomodulation. 2011;18(2):123-30.
29. White LJ, Castellano V, Mc Coy SC. Cytokine responses to resistance training in people with multiple sclerosis. Journal of sports sciences. 2006;24(8):911-4.
30. Åstrand P-O. Textbook of work physiology: physiological bases of exercise: Human Kinetics; 2003.
31. Hotamisligil G. Mechanisms of TNF-alpha-induced insulin resistance. Experimental and clinical endocrinology & diabetes: official journal, German Society of Endocrinology [and] German Diabetes Association. 1998;107(2):119-25.
32. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes research and clinical practice. 2014;105(2):141-50.
33. Zeng Q, Isobe K, Fu L, Ohkoshi N, Ohmori H, Takekoshi K, et al. Effects of exercise on adiponectin and adiponectin receptor levels in rats. Life Sci. 2007;80(5):454-9.
34. Zeng Q, Isobe K, Fu L, Ohkoshi N, Ohmori H, Takekoshi K, et al. Effects of exercise on adiponectin and adiponectin receptor levels in rats. life Sciences. 2007;80(5):454-9.
35. Trapp E, Chisholm D, Freund J, Boutcher S. The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. International journal of obesity. 2008;32(4):684-91.
36. Richards JC, Johnson TK, Kuzma JN, Lonac MC, Schweder MM, Voyles WF, et al. Short‐term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β‐adrenergic stimulation. The Journal of physiology. 2010;588(15):2961-72.
37. Numao S, Katayama Y, Hayashi Y, Matsuo T, Tanaka K. Influence of acute aerobic exercise on adiponectin oligomer concentrations in middle-aged abdominally obese men. Metabolism. 2011;60(2):186-94.
38. Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, et al. Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiovasc Dis. 2010;20(8):608-17.
39. Hopps E, Canino B, Caimi G. Effects of exercise on inflammation markers in type 2 diabetic subjects. Acta Diabetol. 2011;48(3):183-9.
40. Tenorio TRS, Balagopal PB, Andersen LB, Ritti-Dias RM, Hill JO, Lofrano-Prado MC, et al. Effect of Low vs. High Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study. Pediatr Exerc Sci. 2017:1-26.
41. Ostrowski K, Schjerling P, Pedersen BK. Physical activity and plasma interleukin-6 in humans–effect of intensity of exercise. European journal of applied physiology. 2000;83(6):512-5.
42. Trapp EG, Chisholm DJ, Freund J, Boutcher SH. The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. Int J Obes (Lond). 2008;32(4):684-91.
43. Babraj JA, Vollaard NB, Keast C, Guppy FM, Cottrell G, Timmons JA. Extremely short duration high intensity interval training substantially improves insulin action in young healthy males. BMC Endocr Disord. 2009;9:3.
44. Buchan DS, Ollis S, Young JD, Thomas NE, Cooper SM, Tong TK, et al. The effects of time and intensity of exercise on novel and established markers of CVD in adolescent youth. American journal of human biology : the official journal of the Human Biology Council. 2011;23(4):517-26.
45. Hotamisligil G. The role of TNFα and TNF receptors in obesity and insulin resistance. Journal of internal medicine. 1999;245(6):621-5.
61. Yokoyama T, Sekiguchi K, Tanaka T, Tomaru K, Arai M, Suzuki T, et al. Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts. American Journal of Physiology-Heart and Circulatory Physiology. 1999;276(6):H1968-H76.
46. Friedenreich CM, Neilson HK, Woolcott CG, McTiernan A, Wang Q, Ballard-Barbash R, et al. Changes in insulin resistance indicators, IGFs, and adipokines in a year-long trial of aerobic exercise in postmenopausal women. Endocrine-related cancer. 2011;18(3):357-69.
47. Zhaosheng T, Li Y, Chengying G, Yun L, Lian Z. Effect of exercise on the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats. Journal of Huazhong University of Science and Technology [Medical Sciences]. 2005;25(2):191-3.
48. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. The Journal of Clinical Endocrinology & Metabolism. 2001;86(5):1930-5.
49. Kabara E, Sordillo LM, Holcombe S, Contreras GA. Adiponectin links adipose tissue function and monocyte inflammatory responses during bovine metabolic stress. Comparative immunology, microbiology and infectious diseases. 2014;37(1):49-58.
50. Takami K, Takeda N, Nakashima K, Takami R, Hayashi M, Ozeki S, et al. Effects of dietary treatment alone or diet with voglibose or glyburide on abdominal adipose tissue and metabolic abnormalities in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2002;25(4):658-62.