نوع مقاله : مقاله پژوهشی Released under CC BY-NC 4.0 license I Open Access I

نویسندگان

1 دانشجوی کارشناسی ارشد فیزیولوژی ورزشی، دانشکدۀ تربیت بدنی و علوم ورزشی ، دانشگاه مازندران، بابلسر، ایران

2 . دانشیار گروه فیزیولوژی ورزشی، دانشکدة تربیت بدنی و علوم ورزشی، دانشگاه مازندران، بابلسر، ایران

چکیده

دیابت با افزایش لیپوژنز و بیان ژن‌های آن در کبد و فعالیت نئورگولین-4 با تضعیف لیپوژنز کبدی همراه است. هدف پژوهش حاضر بررسی تأثیر 4 هفته تمرین هوازی بر تغییرات سطوح سرمی و کبدی نئورگولین-4 و نیمرخ لیپیدی موش‌های دیابتی بود. 32 سر موش صحرایی نر بالغ، به‌صورت تصادفی به گروه‌های هشت‌تایی کنترل سالم، کنترل دیابتی، تمرین و دیابتی تمرین تقسیم شدند. القای دیابت با تزریق درون‌صفاقی محلول استرپتوزوتوسین (mg/kg 55) انجام گرفت. فرایند تمرین به مدت 4 هفته (5 جلسه در هفته) با سرعت 15 تا 18 متر در دقیقه و برای 25 تا 44 دقیقه اجرا شد. 48 ساعت پس از آخرین جلسۀ تمرینی، خون‌گیری و بافت‌برداری انجام گرفت و سطوح نئورگولین-4 اندازه‌گیری شد. تفاوتی در سطوح سرمی و کبدی نئورگولین-4 بین گروه‌های دیابتی و غیردیابتی مشاهده نشد (05/0<P). سطوح سرمی کلسترول و HDL بین گروه‌های مذکور تفاوت معناداری نداشت (05/0<P). تری‌گلیسرید و LDL بین این گروه‌ها با افزایش معنادار همراه بود (05/0>P). 4 هفته تمرین هوازی بر سطوح سرمی و کبدی نئورگولین-4 موش‌های دیابتی و سالم تأثیری نداشت (05/0<P). همچنین 4 هفته تمرین هوازی بر سطوح سرمی کلسترول، تری‌گلیسرید، HDL و LDL در موش‌های سالم مؤثر نبود (05/0<P). تمرین در موش‌های دیابتی موجب کاهش معنادار سطوح سرمی کلسترول و تری‌گلیسرید شد (05/0>P)، ولی تفاوت معناداری در HDL و LDL ایجاد نکرد (05/0<P). با اینکه سطوح نیمرخ لیپیدی دچار تغییرات محسوس شد، احتمالاً تمرینات ورزشی هوازی در 4 هفته نمی‌تواند محرک افزایش نئورگولین-4 گردشی و بافتی کبد باشد.
 

کلیدواژه‌ها

عنوان مقاله [English]

The Effect of 4 Weeks of Aerobic Exercise on Serum and Liver Levels of Neuregulin-4 in Diabetic Rats

نویسندگان [English]

  • Seyyed Pedram Rouhani Doost 1
  • Rozita Fathi 2

1 MSc Student of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Mazandaran University, Babolsar, Iran

2 Associate Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Mazandaran University, Babolsar, Iran

چکیده [English]

­Diabetes is associated with increased lipogenesis and expression of lipogenic genes in the liver, and neuregulin-4 activity is associated with inhibition of liver lipogenesis. The aim of this study was to investigate the effect of 4 weeks of aerobic exercise on changes of serum and liver levels of neuregulin-4and lipid profile in diabetic rats. ­32 male adult rats were randomly divided into healthy control, control diabetic, exercise and exercise diabetic groups (each group 8 rats). Diabetes was induced by intraperitoneal injection of streptozotocin solution (55 mg/kg). The exercise was performed for 4 weeks, 5 sessions per week, at speeds of 15 to 18 m/min. and for 25 to 44 minutes. 48 hours after the last exercise session, blood samples were collected and liver tissue was removed and Neuregulin-4 levels were measured. The results showed no difference in serum and liver levels of neuregulin-4 between diabetic and healthy groups (P>0.05). Serum levels of cholesterol and HDL were not significantly different among the above groups (P>0.05). Triglyceride and LDL were significantly higher among these groups (P<0.05). 4 weeks of aerobic exercise did not affect serum and liver levels of neuregulin-4 in diabetic and healthy rats (P>0.05). Also, 4 weeks of aerobic exercise did not affect serum levels of cholesterol, triglyceride, HDL and LDL in healthy rats (P>0.05). Exercise in diabetic rats significantly decreased serum levels of cholesterol and triglyceride (P<0.05) but it did not make any significant differences in HDL and LDL (P>0.05). ­Although the levels of lipid profile changed significantly,  4 weeks of aerobic exercise probably cannot stimulate increases of neuregulin-4 in serum and liver tissue.

کلیدواژه‌ها [English]

  • aerobic exercise
  • diabetes
  • lipid profile
  • liver lipogenesis
  • neuregulin-4
1.   Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, et al. Prevalence of diabetes and impaired fasting glucose in adults in the US population: National Health And Nutrition Examination Survey 1999–2002. Diabetes care. 2006;29(6):1263-8.
2.   Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, et al. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes. 2007;56(7):1783-91.
3.   Babaei-Jadidi R, Karachalias N, Kupich C, Ahmed N, Thornalley P. High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia. 2004;47(12):2235-46.
4.   Singh A, Le P, Lopez R, Alkhouri N. The utility of noninvasive scores in assessing the prevalence of nonalcoholic fatty liver disease and advanced fibrosis in type 1 diabetic patients. Hepatology international. 2018:1-7.
5.   Roche E, Farfari S, Witters LA, Assimacopoulos-Jeannet F, Thumelin S, Brun T, et al. Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression. Diabetes. 1998;47(7):1086-94.
6.   Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nature Reviews Endocrinology. 2017;13(1):26-35.
7.   South JC, Blackburn E, Brown IR, Gullick WJ. The neuregulin system of ligands and their receptors in rat islets of langerhans. Endocrinology. 2013;154(7):2385-92.
8.   Wang G-X, Zhao X-Y, Meng Z-X, Kern M, Dietrich A, Chen Z, et al. The brown fat–enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nature medicine. 2014;20(12):1436-43.
9.   Pfeifer A. NRG4: an endocrine link between brown adipose tissue and liver. Cell metabolism. 2015;21(1):13-4.
10. Kang YE, Kim JM, Choung S, Joung KH, Lee JH, Kim HJ, et al. Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes. diabetes research and clinical practice. 2016;117:1-3.
11. Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, et al. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes/metabolism research and reviews. 2017;33(4):1-22.
12. Cai C, Lin M, Xu Y, Li X, Yang S, Zhang H. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC medicine. 2016;14(1):165-72.
13. Hayes NV, Newsam RJ, Baines AJ, Gullick WJ. Characterization of the cell membrane-associated products of the Neuregulin 4 gene. Oncogene. 2008;27(5):715-20.
14. Schneider MR, Wolf E. The epidermal growth factor receptor ligands at a glance. Journal of cellular physiology. 2009;218(3):460-6.
15. Nugroho DB, Ikeda K, Barinda AJ, Wardhana DA, Yagi K, Miyata K, et al. Neuregulin-4 is an angiogenic factor that is critically involved in the maintenance of adipose tissue vasculature. Biochemical and biophysical research communications. 2018.
16. Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes care. 1998;21(1):160-78.
17. Mudalair S, Edelman S, LeRoith D, Taylor S, Olefsky J. Diabetes Mellitus: a Fundamental and Clinical Text. 2000.
18. Connelly MA, Shalaurova I, Otvos JD. High-density lipoprotein and inflammation in cardiovascular disease. Translational Research. 2016;173:7-18.
19. Chahil TJ, Ginsberg HN. Diabetic dyslipidemia. Endocrinology and Metabolism Clinics. 2006;35(3):491-510.
20. Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart J-C, et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science. 2001;294(5540):169-73.
21. Zanuso S, Jimenez A, Pugliese G, Corigliano G, Balducci S. Exercise for the management of type 2 diabetes: a review of the evidence. Acta diabetologica. 2010;47(1):15-22.
22. Broderick TL, Poirier P, Gillis M. Exercise training restores abnormal myocardial glucose utilization and cardiac function in diabetes. Diabetes/metabolism research and reviews. 2005;21(1):44-50.
23. Horton ES. Role and management of exercise in diabetes mellitus. Diabetes care. 1988;11(2):201-11.
24. Boule N, Haddad E, Kenny G, Wells G, Sigal R. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta‐analysis of controlled clinical trials. Scandinavian Journal of Medicine & Science in Sports. 2002;12(1):60-1.
25. Dalia O. Saleh a ARBa, Wafaa I. El-Eraky a, Aiman S. El-Khatib. Streptozotocin-induced vascular and biochemical changes in rats: Effects of rosiglitazone vs. metformin. Bulletin of Faculty of Pharmacy, Cairo University 2013; 51: 131–8.
26. Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. Disease Models & Mechanisms. 2009;2(9-10):454-66.
27. Dabidi Roshan V, Ranjbar S, Hosseinzadeh M, Myers J. Left ventricular oxidant and antioxidant markers induced by lifestyle modification in rats exposed to lead acetate. European Journal of Sport Science. 2012;12(6):485-90.
28. Shirinbayan V, Dabidi Roshan V, Mahjoub S. The therapeutic effect of endurance training on adriamycin-induced cardiac stress in rats. Iranian Journal of Health and Physical Activity. 2013;4(2):8-17.
29. Röhling M, Herder C, Roden M, Stemper T, Müssig K. Effects of long-term exercise interventions on glycaemic control in type 1 and type 2 diabetes: a systematic review. Experimental and Clinical Endocrinology & Diabetes. 2016;124(08):487-94.
30  Riddell MC, Gallen IW, Smart CE, Taplin CE, Adolfsson P, Lumb AN, et al. Exercise management in type 1 diabetes: a consensus statement. The Lancet Diabetes & Endocrinology. 2017;5(5):377-90.
31. Ghanbari-Niaki A. Neuregulins Response to Exercise. 2016.
32. Zhang L, Fu Y, Zhou N, Cheng X, Chen C. Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Endocrine. 2017;57(3):535-8.
33. Khan H, Sobki S, Khan S. Association between glycaemic control and serum lipids profile in type 2 diabetic patients: HbA 1c predicts dyslipidaemia. Clinical and experimental medicine. 2007;7(1):24-9.
34. Guy J, Ogden L, Wadwa RP, Hamman RF, Mayer-Davis EJ, Liese AD, et al. Lipid and Lipoprotein Profiles in Youth with and Without Type 1 Diabetes: The SEARCH Case-Control Study. Diabetes Care. 2008.
35. Thagele SN, Sharma AK, Singh N, Kumar M, Rawat D, Sharma S. Impact of Disease Duration on Lipid Profile in Type 2 Diabetes Mellitus Patients. Hip (cm).100:3.58.
36. Kantharidis P, Wang B, Carew RM, Lan HY. Diabetes complications: the microRNA perspective. Diabetes. 2011;60(7):1832-7.
37. Moeinifard M, Hedayati M. Alloxan and Streptozotocin, Diabetes Research Tool. Applied Sport Physiology Research. 2015;10(20):13-22.
38. WANG Q-a, CAI M-x, TIAN Z-j. Effects of Resistance Training on NRG1 Express of Heart and Skeletal Muscle in Different Gender Rats with Myocardial Infarction. Journal of Beijing Sport University. 2014;11:012.
39. Cai M-X, Shi X-C, Chen T, Tan Z-N, Lin Q-Q, Du S-J, et al. Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model. Life sciences. 2016;149:1-9.
40. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, et al. The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. European heart journal. 2012;35(39):2722-31.
41. LeBrasseur NK, Mizer KC, Parkington JD, Sawyer DB, Fielding RA. The expression of neuregulin and erbB receptors in human skeletal muscle: effects of progressive resistance training. European journal of applied physiology. 2005;94(4):371-5.
42. Ennequin G, Boisseau N, Caillaud K, Chavanelle V, Etienne M, Li X, et al. Neuregulin 1 improves glucose tolerance in db/db mice. PloS one. 2015;10(7):e0130568.
43. Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Medicine. 2014;44(2):211-21.
44. Dengel DR, Hagberg JM, Pratley RE, Rogus EM, Goldberg AP. Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men. Metabolism-Clinical and Experimental. 1998;47(9):1075-82.
45. Durstine JL, Grandjean PW, Cox CA, Thompson PD. Lipids, lipoproteins, and exercise. Journal of Cardiopulmonary Rehabilitation and Prevention. 2002;22(6):385-98.
46. Laaksonen DE, Atalay M, Niskanen LK, Mustonen J, Sen CK, Lakka TA, et al. Aerobic exercise and the lipid profile in type 1 diabetic men: a randomized controlled trial. Medicine and science in sports and exercise. 2000;32(9):1541-8.
47. Gordon LA, Morrison EY, McGrowder DA, Young R, Fraser YTP, Zamora EM, et al. Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes. BMC complementary and alternative medicine. 2008;8(1):21.
48. Mosher PE, Nash MS, Perry AC, LaPerriere AR, Goldberg RB. Aerobic circuit exercise training: effect on adolescents with well-controlled insulin-dependent diabetes mellitus. Archives of physical medicine and rehabilitation. 1998;79(6):652-7.