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


1 PhD student in Exercise Physiology

2 Associate Professor, Shahrekord University

3 Assistant professor, Shahrekord University of Medical Science

4 Assistant professor, Shahrekord University


Aim: NLRP-3 Inflammasome is considered an indicator of chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) which can result in secretion of IL-1β from adipose tissue. Despite numerous investigations on the underlying activation mechanisms of NLRP-3 in pathogenesis of T2DM, less attention has been paid to the impact of exercise on NLRP-3.
Method: Male stereptpzosin-induces diabetic rats (n=40) were randomly assigned to five groups (n=8): diabetic+ low intensity  endurance training (DL), diabetic+ moderate intensity endurance training (DM), diabetic+ high intensity endurance training (DH), non-diabetic with no training(CON), and diabetic with no training(D). Eight weeks of running (four sessions per week) with different intensities were completed. Western blotting method was used to measure NLRP3.  ELISA technique was used to assess serum levels of insulin and glucose.
Results: Results showed that expression of NLRP-3 protein were significantly lower in endurance DM (P<0.05) and endurance DH (P<0.05) groups against DL group. Caspase-1 expression was significantly lower in DL (P=0.001), DM (P<0.05), and DH (P<0.05) compared with D group. However, no significant different was found between the training groups. Serum insulin level was significantly lower in endurance DH group compared with endurance DL group (P<0.05).In comparison with D group, significant reduction of serum glucose was observed in endurance DL group (P<0.05), endurance DM (P<0.05), and endurance DH (P<0.05).
Conclusion: It appears that training with high and moderate intensities induced positive modulation in NLRP-3 expression as well as improved glycemic factors levels.


  1. Shaw JE, Sicree RA, Zimmet PZ. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87:4-14.
  2. Whiting DR, Guariguata L, Weil C, Shaw J. (2011). IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes research and clinical practice, 94:311-21.
  3. Guariguata L. (2012). By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes research and clinical practice, 98:524-5.
  4. Noroozi A, Tahmasebi R, Shaybani B. (2014). Relationship between personality trait and self-management in diabetic patients referred to Bushehr medical centers in 2012-13. ISMJ, 16:436-46.
  5. Ahmadi A, Hasanzadeh J, Rahimi MM, Lashkari L. (2011). Effective factors in the quality of life in patients with type 2 diabetes in chaharmahal & bakhteyari province.
  6. Wang CCL, Hess CN, Hiatt WR, Goldfine AB. (2016). Clinical Update: Cardiovascular Disease in Diabetes Mellitus. Circulation, 133:2459-502.
  7. Shi L, Shu X-O, Li H, Cai H, Liu Q, Zheng W, et al. (2013). Physical activity, smoking, and alcohol consumption in association with incidence of type 2 diabetes among middle-aged and elderly Chinese men. PloS one, 8:77919.
  8. Donath MY, Shoelson SE. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology, 11:98-107.
  9. Goossens GH, Blaak EE, Theunissen R, Duijvestijn AM, Clément K, Tervaert J-WC, et al. (2012). Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. Molecular immunology, 50:142-9.
  10. Melo LC, Dativo-Medeiros J, Menezes-Silva CE, Barbosa FT, Sousa-Rodrigues CFd, Rabelo LA. (2017). Physical exercise on inflammatory markers in type 2 diabetes patients: a systematic review of randomized controlled trials. Oxidative Medicine And Cellular Longevity.
  11.  Ouchi N, Parker JL, Lugus JJ, Walsh K. (2011). Adipokines in inflammation and metabolic disease. Nature Reviews Immunology.11:85-97.
  12. Vandanmagsar B, Youm Y-H, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. (2011). The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature medicine, 17:179-88.
  13. Koenen TB, Stienstra R, Van Tits LJ, De Graaf J, Stalenhoef AF, Joosten LA, et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1β transcription in human adipose tissue. Diabetes. 2011;60(2):517-24.
  14. Zhang X, Dai J, Li L, Chen H, Chai Y. (2017). NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages. Journal of diabetes research.
  15. Rheinheimer J, de Souza BM, Cardoso NS, Bauer AC, Crispim D.(2017). Current role of the NLRP3 inflammasome on obesity and insulin resistance: a systematic review. Metabolism.
  16. Shao B-Z, Xu Z-Q, Han B-Z, Su D-F, Liu C. (2015). NLRP3 inflammasome and its inhibitors: a review. Frontiers in pharmacology. 6.
  17. Davis BK, Wen H, Ting JP-Y. (2011) The inflammasome NLRs in immunity, inflammation, and associated diseases. Annual review of immunology, 29:707-35.
  18. De Nardo D, Latz E. (2011). NLRP3 inflammasomes link inflammation and metabolic disease. Trends in immunology.32:373-9.
  19. Dixit VD. (2013). Nlrp3 inflammasome activation in type 2 diabetes: is it clinically relevant? Diabetes, 62:22-4.
  20. Mardare C, Krüger K, Liebisch G, Seimetz M, Couturier A, Ringseis R, et al. (2015). Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice. Journal of diabetes research.
  21. Mejías-Peña Y, Estébanez B, Rodriguez-Miguelez P, Fernandez-Gonzalo R, Almar M, de Paz JA, et al. (2017). Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects. Aging (Albany NY), 9(2):408.
  22. de Paula Martins R, Lim CK, Ghisoni K, Staats A, Dallagnol K, Solano A, et al. (2016). Treating depression with exercise: The inflammasome inhibition perspective.
  23. Wang Y, Xu Y, Sheng H, Ni X, Lu J. (2016). Exercise amelioration of depression-like behavior in OVX mice is associated with suppression of NLRP3 inflammasome activation in hippocampus. Behavioural brain research, 307:18-24.
  24. Ringseis R, Eder K, Mooren FC, Krüger K. (2015). Metabolic signals and innate immune activation in obesity and exercise. Exercise immunology review, 21.
  25. Chen L, Pei J-H, Kuang J, Chen H-M, Chen Z, Li Z-W, et al. (2015). Effect of lifestyle intervention in patients with type 2 diabetes: a meta-analysis. Metabolism, 64(2):338-47.
  26. Schwingshackl L, Missbach B, Dias S, König J, Hoffmann G. (2014). Impact of different training modalities on glycaemic control and blood lipids in patients with type 2 diabetes: a systematic review and network meta-analysis. Springer.
  27. Jelleyman C, Yates T, O'Donovan G, Gray LJ, King JA, Khunti K, et al. (2015). The effects of high‐intensity interval training on glucose regulation and insulin resistance: a meta‐analysis. Obesity reviews, 16(11):942-61.
  28. Aamot IL, Karlsen T, Dalen H, Støylen A. (2016). Long‐term Exercise Adherence After High‐intensity Interval Training in Cardiac Rehabilitation: A Randomized Study. Physiotherapy Research International, 21:54-64.
  29. El-Kader SA, Gari A, El-Den AS. (2013). Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial. African health sciences, 13:857-63.
  30. Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, et al. (2010). 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. Nutrition, Metabolism and Cardiovascular Diseases, 20(8):608-17.
  31. Kim JS, Lee YH, Kim JC, Ko YH, Yoon CS, Yi HK.(2014). Effect of exercise training of different intensities on anti-inflammatory reaction in streptozotocin-induced diabetic rats. Biology of sport, 31:73.
  32. Tenório TR, Balagopal PB, Andersen LB, Ritti-Dias RM, Hill JO, Lofrano-Prado MC, et al. (2017). 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. Pediatric Exercise Science, 1-26.
  33. Marinho R, Moura LPd, Rodrigues BdA, Pauli LSS, Silva ASRd, Ropelle ECC, et al. (2014). Effects of different intensities of physical exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice. Einstein (São Paulo), 12(1):82-9.
  34. Da Silva A, Pauli JR, Ropelle ER, Oliveira AG, Cintra DE, De Souza CT, et al. (2010). Exercise intensity, inflammatory signaling, and insulin resistance in obese rats. Medicine and science in sports and exercise, 42(12):2180-8.
  35. Kim D-H, Kim S-H, Kim W-H, Moon C-R. (2013). The effects of treadmill exercise on expression of UCP-2 of brown adipose tissue and TNF-α of soleus muscle in obese Zucker rats. Journal of Exercise Nutrition & Biochemistry, 17(4):199.
  36. Pushparaj P, Low H, Manikandan J, Tan B, Tan C. (2007). Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology, 111(2):430-4.
  37. Freigang S, Ampenberger F, Weiss A, Kanneganti T-D, Iwakura Y, Hersberger M, et al. (2013). Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1 [alpha] and sterile vascular inflammation in atherosclerosis. Nature immunology, 14(10):1045-53.
  38.           Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, et al. (2011). Inflammasome is a central player in the induction of obesity and insulin resistance. Proceedings of the National Academy of Sciences, 108:15324-9.
  39. Stienstra R, Tack CJ, Kanneganti T-D, Joosten LA, Netea MG. (2012). The inflammasome puts obesity in the danger zone. Cell metabolism, 15:8-10.
  40. Grant RW, Dixit VD. (2013). Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Frontiers in immunology, 4.
  41. He Y, Franchi L, Núñez G. (2013). TLR agonists stimulate Nlrp3-dependent IL-1β production independently of the purinergic P2X7 receptor in dendritic cells and in vivo. The Journal of Immunology, 190(1):334-9.
  42. Snodgrass RG, Huang S, Choi I-W, Rutledge JC, Hwang DH. (2013). Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids. The Journal of Immunology, 191(8):4337-47.
  43. Oliveira AG, Carvalho BM, Tobar N, Ropelle ER, Pauli JR, Bagarolli RA, et al. (2011). Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes, 60(3):784-96.
  44. Hong J, Kim K, Kim J-H, Park Y. (2017). The Role of Endoplasmic Reticulum Stress in Cardiovascular Disease and Exercise. International Journal of Vascular Medicine.



  1.           Fujitani Y, Kawamori R, Watada H. (2009). The role of autophagy in pancreatic β-cell and diabetes. Autophagy, 5(2):280-2.
  2. .         Chen R-J, Lee Y-H, Yeh Y-L, Wang Y-J, Wang Jr B. (2016). The Roles of Autophagy and the Inflammasome during Environmental Stress-Triggered Skin Inflammation. International journal of molecular sciences, 17(12):2063.
  3. .         Xia S, Zhang X, Zheng S, Khanabdali R, Kalionis B, Wu J, et al. (2016). An update on inflamm-aging: mechanisms, prevention, and treatment. Journal of immunology research.
  4. .         Salminen A, Kaarniranta K, Kauppinen A. (2013). Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing research reviews, 12(2):520-34.
  5. Vainshtein A, Grumati P, Sandri M, Bonaldo P. (2014). Skeletal muscle, autophagy, and physical activity: the ménage à trois of metabolic regulation in health and disease. Journal of molecular medicine, 92(2):127-37.
  6. .         Mejías-Peña Y, Rodriguez-Miguelez P, Fernandez-Gonzalo R, Martínez-Flórez S, Almar M, de Paz JA, et al. (2016). Effects of aerobic training on markers of autophagy in the elderly. Age, 38(2):33.
  7.           Brinkmann C, Przyklenk A, Metten A, Schiffer T, Bloch W, Brixius K, et al. (2017). Influence of endurance training on skeletal muscle mitophagy regulatory proteins in type 2 diabetic men. Endocrine Research., 1-6.
  8. .         Kim M-J, Yoon J-H, Ryu J-H. (2016). Mitophagy: a balance regulator of NLRP3 inflammasome activation. BMB reports, 49(10):529.
  9. .         Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, et al. (2011). Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. Journal of applied physiology, 111(6):1554-60.
  10. .         Phielix E, Meex R, Moonen-Kornips E, Hesselink M, Schrauwen P. (2010).  Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals. Diabetologia, 53(8):1714-21.
  11. .         Dube J, Amati F, Toledo F, Stefanovic-Racic M, Rossi A, Coen P, et al. (2011).  Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia, 54(5):1147-56.
  12. .         Taniguchi CM, Emanuelli B, Kahn CR. (2006). Critical nodes in signalling pathways: insights into insulin action. Nature reviews Molecular cell biology, 7(2):85-96.
  13.           Błachnio-Zabielska A, Zabielski P, Baranowski M, Gorski J. (2011). Aerobic training in rats increases skeletal muscle sphingomyelinase and serine palmitoyltransferase activity, while decreasing ceramidase activity. Lipids, 46(3):229-38.
  14. .         Kawanishi N, Yano H, Yokogawa Y, Suzuki K. (2010). Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exercise immunology review, 16.
  15. .         Mardare C, Krüger K, Liebisch G, Seimetz M, Couturier A, Ringseis R, et al. (2016). Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice. Journal of diabetes research.
  16. .         El-Kader SMA, Al-Shreef FM. (). Biomarkers of endothelial function and insulin resistance response to aerobic exercise versus resisted exercises in obese type 2 diabetic patients.
  17. .         Ouerghi N, Fradj MKB, Bezrati I, Feki M, Kaabachi N, Bouassida A. (2017). Effect of High-Intensity Interval Training on Plasma Omentin-1 Concentration in Overweight/Obese and Normal-Weight Youth. Obesity Facts, 10(4):323-31.
  18. Shakil-ur-Rehman S, Karimi H, Gillani SA. (2017). Effects of supervised structured aerobic exercise training program on fasting blood glucose level, plasma insulin level, glycemic control, and insulin resistance in type 2 diabetes mellitus. Pakistan journal of medical sciences, 33(3):576.
  19. .         Afshounpour MT, Habibi A, Ranjbar R. (2016). Impact of combined exercise training on plasma concentration of Apelin, resistin and insulin resistance in patients with type 2 diabetics’ male. Bimonthly Journal of Hormozgan University of Medical Sciences, 20(3):158-69.
  20. .         Pereira RM, Moura LPd, Muñoz VR, Silva ASRd, Gaspar RS, Ropelle ER, et al. (2017). Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise. Motriz: Revista de Educação Física, 23.
  21. .         Sylow L, Kleinert M, Richter EA, Jensen TE. (2017).  Exercise-stimulated glucose uptake [mdash] regulation and implications for glycaemic control. Nature Reviews Endocrinology, 3:133-148.
  22. .         Merry TL, McConell GK. (2009). Skeletal muscle glucose uptake during exercise: a focus on reactive oxygen species and nitric oxide signaling. IUBMB life, 61(5):479-84.
  23. .         Richter EA, Hargreaves M. (2013). Exercise, GLUT4, and skeletal muscle glucose uptake. Physiological reviews, 93(3):993-101.