The Effect of Aerobic Exercise and Quercetin Supplementation on Myostatin and Follistatin Levels in the Heart Tissue of Rats with Type 2 Diabetes

Soltani, Mohsen; Barzegari, Ali; Naghibi, Saeed; Dashty khavidaki, Mohammad hassaan

doi:10.61186/jsmt.21.26.1

Volume 21, Issue 26 (12-2023) RSMT 2023, 21(26): 1-17 | Back to browse issues page

‎ 10.61186/jsmt.21.26.1

Mendeley

Zotero

RefWorks

Soltani M, Barzegari A, Naghibi S, Dashty khavidaki M H. The Effect of Aerobic Exercise and Quercetin Supplementation on Myostatin and Follistatin Levels in the Heart Tissue of Rats with Type 2 Diabetes. RSMT 2023; 21 (26) :1-17
URL: http://jsmt.khu.ac.ir/article-1-528-en.html

The Effect of Aerobic Exercise and Quercetin Supplementation on Myostatin and Follistatin Levels in the Heart Tissue of Rats with Type 2 Diabetes

Mohsen Soltani

, Ali Barzegari

, Saeed Naghibi

, Mohammad hassaan Dashty khavidaki

Payame Noor University & Assistant professor Payame Noor University ,Department of Physical Education ,Payame Noor University, Tehran, Iran , ali_barzegari@pnu.ac.ir

Abstract: (2694 Views)

This study aimed to investigate the effect of quercetin supplementation and training on myostatin and follistatin levels in the heart tissue of diabetic rats. Methods: For this purpose, 50 10-week-old male Wistar rats with an average weight of 237±33 grams were randomly divided into five groups of 10 including: healthy control, diabetes, diabetes+supplement, diabetes+exercise, and diabetes+supplement+exercise. . The training protocol includes five sessions per week for eight weeks on a treadmill without a special slope. The rodents ran for 60 minutes at a speed of 25 meters per minute in each session.and the supplement groups received 50 mg/kg quercetin daily by gavage. The results showed that the difference in myostatin levels among the groups is significant (P=0.001). There was a significant decrease in myostatin levels between exercise+supplement+diabetes group with diabetes (P=0.002). There was also a significant difference between the supplement+diabetes and exercise+diabetes groups (P=0.009). Also, the results showed that the difference in follistatin levels among the groups is significant (P=0.001). The results showed that follistatin levels in the heart tissue increased significantly between the groups of diabetes, exercise+diabetes, supplement+diabetes and exercise+supplements+diabetes with the control group (respectively: P=0.005; P=0.001; P=0.001; P = 0.001).
It seems that moderate intensity aerobic exercise and quercetin supplementation have a positive and beneficial effect on the levels of myostatin and folstatin.

Keywords: Exercise, Diabetes, Follistatin, Myostatin

Full-Text [PDF 2209 kb] (507 Downloads)

Type of Study: Research | Subject: sport physiology
Received: 2022/04/14 | Accepted: 2023/05/29 | Published: 2023/12/31

References

1. Antosik K, Borowiec M. Genetic Factors of Diabetes. Archivum immunologiae et therapiae experimentalis. 2016;64(Suppl 1):157-60. [DOI:10.1007/s00005-016-0432-8]

2. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes research and clinical practice. 2010;87(1):4-14. [DOI:10.1016/j.diabres.2009.10.007]

3. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes care. 2004;27(5):1047-53. [DOI:10.2337/diacare.27.5.1047]

4. Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes research and clinical practice. 2012;98(3):524-5. [DOI:10.1016/j.diabres.2012.11.006]

5. Camarca ME, Mozzillo E, Nugnes R, Zito E, Falco M, Fattorusso V, et al. Celiac disease in type 1 diabetes mellitus. Italian journal of pediatrics. 2012;38(1):1-7. [DOI:10.1186/1824-7288-38-10]

6. Association AD. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014;37(Supplement_1):S81-S90. [DOI:10.2337/dc14-S081]

7. Chen L, Chen R, Wang H, Liang F. Mechanisms linking inflammation to insulin resistance. International journal of endocrinology. 2015;2015. [DOI:10.1155/2015/508409]

8. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. The Lancet. 2014;383(9922):1068-83. [DOI:10.1016/S0140-6736(13)62154-6]

9. Balducci S, Zanuso S, Cardelli P, Salvi L, Mazzitelli G, Bazuro A, et al. Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of body weight loss in subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES). Diabetes Care. 2012;35(6):1347-54. [DOI:10.2337/dc11-1859]

10. Belfiore A, Malaguarnera R. Insulin receptor and cancer. Endocrine-related cancer. 2011;18(4):R125-R47. [DOI:10.1530/ERC-11-0074]

11. Jones M, Wilson S, Mullin B, Mead R, Watts G, Stuckey B. Polymorphism of the follistatin gene in polycystic ovary syndrome. MHR: Basic science of reproductive medicine. 2007;13(4):237-41. [DOI:10.1093/molehr/gal120]

12. Sidis Y, Mukherjee A, Keutmann H, Delbaere A, Sadatsuki M, Schneyer A. Biological activity of follistatin isoforms and follistatin-like-3 is dependent on differential cell surface binding and specificity for activin, myostatin, and bone morphogenetic proteins. Endocrinology. 2006;147(7):3586-97. [DOI:10.1210/en.2006-0089]

13. Grusch M, Drucker C, Peter-Vörösmarty B, Erlach N, Lackner A, Losert A, et al. Deregulation of the activin/follistatin system in hepatocarcinogenesis. Journal of hepatology. 2006;45(5):673-80. [DOI:10.1016/j.jhep.2006.06.014]

14. Lambert-Messerlian G, Eklund E, Pinar H, Tantravahi U, Schneyer AL. Activin subunit and receptor expression in normal and cleft human fetal palate tissues. Pediatric and Developmental Pathology. 2007;10(6):436-45. [DOI:10.2350/06-05-0087.1]

15. Jones KL, Mansell A, Patella S, Scott BJ, Hedger MP, de Kretser DM, et al. Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. Proceedings of the National Academy of Sciences. 2007;104(41):16239-44. [DOI:10.1073/pnas.0705971104]

16. Hansen J, Rinnov A, Krogh‐Madsen R, Fischer C, Andreasen A, Berg R, et al. Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low‐grade inflammation. Diabetes/metabolism research and reviews. 2013;29(6):463-72. [DOI:10.1002/dmrr.2415]

17. de Kretser DM, O'Hehir RE, Hardy CL, Hedger MP. The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Molecular and cellular endocrinology. 2012;359(1-2):101-6. [DOI:10.1016/j.mce.2011.10.009]

18. Fife E, Kostka J, Kroc Ł, Guligowska A, Pigłowska M, Sołtysik B, et al. Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men. BMC geriatrics. 2018;18(1):1-10. [DOI:10.1186/s12877-018-0888-y]

19. Karami M, Hosseini SM. Prevalence of chronic complications and related risk factors of diabetes in patients referred to the diabetes center of Hamedan Province. Avicenna Journal of Nursing and Midwifery Care. 2017;25(2):69-74. [DOI:10.21859/nmj-25029]

20. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee I-M, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medicine and science in sports and exercise. 2011;43(7):1334-59. [DOI:10.1249/MSS.0b013e318213fefb]

21. Matsakas A, Bozzo C, Cacciani N, Caliaro F, Reggiani C, Mascarello F, et al. Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats. Experimental physiology. 2006;91(6):983-94. [DOI:10.1113/expphysiol.2006.033571]

22. Xi Y, Gong D-W, Tian Z. FSTL1 as a potential mediator of exercise-induced cardioprotection in post-myocardial infarction rats. Scientific reports. 2016;6(1):1-11. [DOI:10.1038/srep32424]

23. toloueiazar j, Tofighi A, alizadeh r. The Effect of High Intensity Interval Training on Serum Levels of FGF21, Insulin Resistance and Lipid Profile in Sedentary Obese Women. Journal of Sport Biosciences. 2019;10(4):449-64.

24. Azhir S, Alijani E, Mohsenzadeh M. Effect of 8 weeks HIIT exercise on myostatin, follistatin an follistatin gene expression ratios on myostatin in male rats with type 2 diabetes. Majallah-i pizishki-i Danishgah-i Ulum-i Pizishki va Khadamat-i Bihdashti-i Darmani-i Tabriz. 2020;42(2):117-25. [DOI:10.34172/mj.2020.027]

25. Biglari S, Gaeini AA, Kordi MR, Ghardashi Afousi A. The effect of 8 weeks high-intensity interval training on myostatin and follistatin gene expression in gastrocnemius muscle of the rats. Journal of Arak University of Medical Sciences. 2018;21(1):1-10.

26. Asgharpour F, Pouramir M, Moghadamnia A. Evaluation of viscosity of traditional medicinal antihyperglycemic plant extracts and relationship with glucose diffusion in vitro. Journal of Medicinal Plants. 2012;11(41):166-76.

27. Shi G-J, Li Y, Cao Q-H, Wu H-X, Tang X-Y, Gao X-H, et al. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: A systematic review of the literature. Biomedicine & Pharmacotherapy. 2019;109:1085-99. [DOI:10.1016/j.biopha.2018.10.130]

28. Ebrahimpour S, Zakeri M, Esmaeili A. Crosstalk between obesity, diabetes, and alzheimer's disease: Introducing quercetin as an effective triple herbal medicine. Ageing research reviews. 2020;62:101095. [DOI:10.1016/j.arr.2020.101095]

29. Mythili MD, Vyas R, Akila G, Gunasekaran S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microscopy research and technique. 2004;63(5):274-81. [DOI:10.1002/jemt.20039]

30. Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. Disease models & mechanisms. 2009;2(9-10):454-66. [DOI:10.1242/dmm.001941]

31. rezaee s, barari a, ahmadi m. Effect of eight weeks aerobic training on the levels of antioxidant enzymes in the heart tissue of type 2 diabetic rats. 2020;13(4):49-60.

32. Lenk K, Erbs S, Höllriegel R, Beck E, Linke A, Gielen S, et al. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. European journal of preventive cardiology. 2012;19(3):404-11. [DOI:10.1177/1741826711402735]

33. Beigi M, Jamshid B, Saeed K, Hamid Z. The Effect of a Period of Moderate Endurance Training and High Interval Training on Activin Receptor Type II in Heart, and Plasma Levels of Myostatin in Male Rats. JOURNAL OF ISFAHAN MEDICAL SCHOOL (IUMS). 2019;37(544):1111.

34. Slimestad R, Fossen T, Vågen IM. Onions: a source of unique dietary flavonoids. Journal of agricultural and food chemistry. 2007;55(25):10067-80. [DOI:10.1021/jf0712503]

35. De Blasio MJ, Huynh N, Deo M, Dubrana LE, Walsh J, Willis A, et al. Defining the progression of diabetic cardiomyopathy in a mouse model of type 1 diabetes. Frontiers in Physiology. 2020;11:124. [DOI:10.3389/fphys.2020.00124]

36. Jokar M, Amirahmadi M, Sherafati Moghadam M. The effect of endurance training on the content of myostatin and SMAD2/3 proteins in the left ventricular tissue of heart muscle of type 1 diabetic rats.. Iranian Journal of Diabetes and Lipid Disorders. 2021;20(3):191-9.

37. Rashidlamir A, Attarzadeh Hosseini SR, Hejazi K, Motevalli Anberani SM. The effect of eight weeks resistance and aerobic training on myostatin and follistatin expression in cardiac muscle of rats. Journal of cardiovascular and thoracic research. 2016;8(4):164-9. [DOI:10.15171/jcvtr.2016.33]

38. Wang S-Q, Li D, Yuan Y. Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway. The Journal of Physiological Sciences. 2019;69(6):861-73. [DOI:10.1007/s12576-019-00696-3]

39. Phillips SA, Mahmoud AM, Brown MD, Haus JM. Exercise interventions and peripheral arterial function: implications for cardio-metabolic disease. Progress in cardiovascular diseases. 2015;57(5):521-34. [DOI:10.1016/j.pcad.2014.12.005]

40. Wang R, Jiao H, Zhao J, Wang X, Lin H. Glucocorticoids enhance muscle proteolysis through a myostatin-dependent pathway at the early stage. PloS one. 2016;11(5):e0156225. [DOI:10.1371/journal.pone.0156225]

41. McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R. Myostatin negatively regulates satellite cell activation and self-renewal. The Journal of cell biology. 2003;162(6):1135-47. [DOI:10.1083/jcb.200207056]

42. Wolfman NM, McPherron AC, Pappano WN, Davies MV, Song K, Tomkinson KN, et al. Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases. Proceedings of the National Academy of Sciences. 2003;100(26):15842-6. [DOI:10.1073/pnas.2534946100]

43. Zhang J, Cao L, Wang W, Huo Y, Zheng Y, Wu F, et al. Protective effect of antioxidants on cardiac function in adult offspring exposed to prenatal overnutrition. Journal of Developmental Origins of Health and Disease. 2022:1-9. [DOI:10.1017/S2040174422000095]

44. Seo M-J, Lee Y-J, Hwang J-H, Kim K-J, Lee B-Y. The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling. The Journal of Nutritional Biochemistry. 2015;26(11):1308-16. [DOI:10.1016/j.jnutbio.2015.06.005]

45. Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity. 2008;16(9):2081-7. [DOI:10.1038/oby.2008.315]

46. Kim C, Hwang J-K. Flavonoids: nutraceutical potential for counteracting muscle atrophy. Food Sci Biotechnol. 2020;29(12):1619-40. [DOI:10.1007/s10068-020-00816-5]

47. Lenk K, Schur R, Linke A, Erbs S, Matsumoto Y, Adams V, et al. Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. European journal of heart failure. 2009;11(4):342-8. [DOI:10.1093/eurjhf/hfp020]

48. Hansen J, Brandt C, Nielsen AR, Hojman P, Whitham M, Febbraio MA, et al. Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine. Endocrinology. 2011;152(1):164-71. [DOI:10.1210/en.2010-0868]

49. Dutra DB, Bueno PG, Silva RN, Nakahara NH, Selistre‐Araújo HS, Nonaka KO, et al. Expression of myostatin, myostatin receptors and follistatin in diabetic rats submitted to exercise. Clinical and Experimental Pharmacology and Physiology. 2012;39(5):417-22. [DOI:10.1111/j.1440-1681.2012.05690.x]

50. Farzanegi P, Zamani M, Khalili A, Dehghani H, Fotohi R, Ghanbarpour MR, et al. Effects of upper- and lower-extremity resistance training on serum vascular endothelial growth factor, myostatin, endostatin and follistatin levels in sedentary male students. Science & Sports. 2021;36(2):139.e1-.e6. [DOI:10.1016/j.scispo.2020.02.013]

51. Khanjani H, Esmaelzadeh Toloee M. The effect of six weeks of high-intensity interval training (HIIT) and endurance on blood glucose and Follistatin protein content in the left ventricular tissue of the heart of male rats with type 1 diabetes. Journal of Sport Biosciences. 2021;13(3):351-65.

52. REZVANI RAD M, Daryanoosh F, Hemmatinafar M, Jamhiri I. The Effect of Consumption of Quercetin Supplement on Gene Expression of PGC-1α during Sedentary Period in Active Rats after a HIIT Course. Sport Physiology & Management Investigations. 2019;11(2):53-62.

53. Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2009;296(4):R1071-R7. [DOI:10.1152/ajpregu.90925.2008]

54. Mafi F, Gaeini A, Kordi M, Biglari S, Sarabi S, Honarmand nasab Y. Comparison of the effect of dark chocolate extract supplementation with eight weeks resistance training on plasma Follistatin level in older adults. Journal of Gerontology. 2018;2(4):64-72. [DOI:10.29252/joge.2.3.64]

55. Woo J. Sarcopenia. Clinics in geriatric medicine. 2017;33(3):305-14. [DOI:10.1016/j.cger.2017.02.003]