اثر تمرین هوازی و امگا-3 بر بیان عوامل اتصالی تکراری تلومر 1 و 2، آنزیم تلومراز ترانس کریپتاز معکوس بافت قلب موش‌های سالمند تغذیه‌شده با رژیم غذایی پرچرب

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران

چکیده

زمینه و هدف: پیری فرایند فیزیولوژیکی پیچیده و شامل از دست دادن پیش‌رونده در عملکرد بدن و تخریب DNA زنجیره‌ای واقع در انتهای کروموزوم‌ها-تلومرهاست. ظرفیت سلول‌ها برای تقسیم با طول تلومر تعیین می‌شود، زیرا کوتاه شدن بیش از حد تلومرها موجب پیری سلولی می‌شود. فعالیت ورزشی و امگا-3 با تأثیر بر تلومرازها از کوتاه شدن تلومرها جلوگیری می‌کند. هدف از تحقیق حاضر بررسی اثر تمرین هوازی همراه با امگا-3 بر برخی شلترین‌ها و تلومرازهای بافت قلب در موش‌های سالمند تغذیه‌شده با رژیم غذایی پرچرب بود.
مواد و روش‌ها: در این تحقیق تجربی، 40 سر موش صحرایی نر نژاد ویستار (میانگین وزن 95/26±32/311 گرم) از انستیتو پاستور تهیه و به آزمایشگاه منتقل شد. پس از انتقال موش‌های صحرایی به آزمایشگاه، به‌طور تصادفی به پنج گروه رژیم غذایی عادی (ND)، رژیم غذایی پرچرب (HFD)، رژیم غذایی پرچرب-تمرین (HFDT)، رژیم غذایی پرچرب- امگا-3 (HFDω3)، تمرین-رژیم غذایی پرچرب-امگا-3 (HFDTω3) تقسیم شدند. القای HFD با استفاده از غذای پرچرب شامل 17 درصد پروتئین، 43 درصد کربوهیدرات و 40 درصد چربی انجام گرفت. گروه‌های مکمل، طی دورة مداخله روزانه 1 گرم امگا-3 (به ازای هر کیلوگرم وزن بدن) را به‌صورت خوراکی دریافت کردند. برنامة تمرین هوازی در شروع شامل دویدن روی نوار گردان با سرعت 10 متر در دقیقه، شیب صفر درجه، به مدت 15 دقیقه بود. سرعت و مدت زمان به‌تدریج به 16 متر در دقیقه و 50 دقیقه در آخرین جلسه افزایش یافت. دویدن به مدت هشت هفته و پنج ‌روز هفته اجرا شد. داده‌ها به روش تحلیل واریانس یکطرفه و آزمون تعقیبی توکی در سطح معناداری 05/0P< تجزیه‌وتحلیل شد.
نتایج: القای HFD موجب کاهش معناداری در بیان TRF2 (002/0=P)، TERT (024/0=P) و افزایش TRF1 (0001/0=P) نسبت به گروه ND شد. تمرین و امگا-3 موجب افزایش معناداری بیان TRF2 و TERT در موش‌های صحرایی HFD شد (05/0P<). همچنین میزان تغییرات بیان TRF2 و TERT در گروه HFDTω3 نسبت به گروه HFDT ( به‌ترتیب 023/0P= و 044/0P=) و HFDω3 (021/0P= و 042/0P=) بیشتر بود.
نتیجه‌گیری: نتایج نشان داد که افزایش سن و HFD با کاهش TRF2، TERT و افزایش TRF1 بافت قلب همراه است و فعالیت ورزشی هوازی و مصرف امگا-3 قادر است این روند را معکوس کند. با توجه به نقش شلترین‌ها و تلومرازها در عملکرد سلولی، به نظر تغییر سطوح این شاخص‌ها در پی فعالیت بدنی و استفاده از مکمل امگا-3 می‌تواند تا حدی از بروز بسیاری از بیماری‌های قلبی ناشی از افزایش سن و چاقی جلوگیری کند.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of aerobic exercise and omega-3 on the expression of telomeric repeat binding factor 1 and 2 and telomerase reverse transcriptase enzyme in the heart tissue of elderly HFD rats

نویسندگان [English]

  • Ghasem Torabi Palat Kaleh
  • Ahmad Abdi
  • Asieh Abbassi Daloii
Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
چکیده [English]

Background and Purpose: Aging is a complex physiological process that involves progressive loss of body function and degradation of DNA strands located at the ends of chromosomes-telomeres. The capacity of cells to divide is determined by telomere length, as an excessive shortening of telomeres causes cellular senescence. Exercise training and omega-3 prevent the shortening of telomeres by affecting telomerase. The aim of the present study was to investigate the effect of aerobic training with omega-3 on some shelterins and telomerase of heart tissue in elderly high-fat diet rats.
Materials and Methods: In this experimental study, 40 male Wistar rats (mean±SD weight, 311.3±26.95 g) were obtained from the Pasteur Institute and transferred to the laboratory. After transferring the rats to the laboratory, they were randomly divided into five groups: Normal Diet (ND), High-Fat Diet (HFD), High-Fat Diet-Training (HFDT), High-Fat Diet-Omega3 (HFDω3), and High-Fat Diet-Training-Omega3 (HFDTω3). HFD induction was performed using a high-fat diet containing 17% protein, 43% carbohydrate, and 40% fat. The supplement groups received 1 g of Omega3 (per kg of body weight) orally during the intervention period. The aerobic exercise training program at the beginning consisted of running on a treadmill at a speed of 10 m/min, 0-degree incline, for 15 minutes. The speed and duration gradually increased to 16 meters per minute and 50 minutes in the last session. Running was carried out for 8 weeks and five days a week. Data were analyzed by one-way analysis of variance and Tukey's post hoc test at the P<0.05.
Results: Induction of HFD significantly decreased the expression of telomeric repeat binding factor 2 (TRF2) (P=0.002), telomerase reverse transcriptase enzyme (TERT) (P=0.024) and increased TRF1 (P=0.0001) compared to the ND group. Exercise and omega-3 significantly increased the expression of TRF2 and TERT in HFD rats (P<0.05). Moreover, TRF2 and TERT expression changes were higher in the HFDTω3 group compared to HFDT (P=0.023 and P=0.044, respectively) and HFDω3 groups (P=0.021 and P=0.042, respectively).
Conclusion: The results of the present study showed that aging and HFD are associated with a decrease in TRF2, TERT and an increase in TRF1 in heart tissue, and aerobic exercise and omega-3 consumption can reverse this trend. Considering the role of shelterins and telomerase in cellular function, it seems that changing the levels of these indicators following physical activity and using omega-3 supplements can partially prevent the occurrence of many heart diseases caused by aging and obesity.
 

کلیدواژه‌ها [English]

  • Exercise
  • Omega 3
  • Shelterin
  • Aging and Obesity
  1. Holohan B, Wright WE, Shay JW. Telomeropathies: An emerging spectrum disorder. Journal of Cell Biology. 2014;205(3):289-99.
  2. Mundstock E, Sarria EE, Zatti H, Mattos Louzada F, Kich Grun L, Herbert Jones M, et al. Effect of obesity on telomere length: systematic review and meta‐analysis. Obesity. 2015;23(11):2165-74.
  3. Schmidt JC, Dalby AB, Cech TR. Identification of human TERT elements necessary for telomerase recruitment to telomeres. Elife. 2014;3:e03563.
  4. Sfeir A, De Lange T. Removal of shelterin reveals the telomere end-protection problem. Science. 2012;336(6081):593-7.
  5. Denham J, O’Brien BJ, Charchar FJ. Telomere length maintenance and cardio-metabolic disease prevention through exercise training. Sports medicine. 2016;46(9):1213-37.
  6. Semeraro MD, Beltrami AP, Kharrat F, Almer G, Sedej S, Renner W, et al. The impact of moderate endurance exercise on cardiac telomeres and cardiovascular remodeling in obese rats. Frontiers in Cardiovascular Medicine. 2023;9:3714.
  7. Werner C, Fürster T, Widmann T, Pöss J, Roggia C, Hanhoun M, et al. Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall. Circulation. 2009;120(24):2438-47.
  8. Cherkas LF, Hunkin JL, Kato BS, Richards JB, Gardner JP, Surdulescu GL, et al. The association between physical activity in leisure time and leukocyte telomere length. Archives of internal medicine. 2008;168(2):154-8.
  9. Denham J, Sellami M. Exercise training increases telomerase reverse transcriptase gene expression and telomerase activity: A systematic review and meta-analysis. Ageing Research Reviews. 2021;70:101411.
  10. Ludlow AT, Witkowski S, Marshall MR, Wang J, Lima LC, Guth LM, et al. Chronic exercise modifies age-related telomere dynamics in a tissue-specific fashion. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2012;67(9):911-26.
  11. Friedenreich CM, Wang Q, Ting NS, Brenner DR, Conroy SM, McIntyre JB, et al. Effect of a 12-month exercise intervention on leukocyte telomere length: Results from the ALPHA Trial. Cancer Epidemiology. 2018;56:67-74.
  12. Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. Jama. 2010;303(3):250-7.
  13. Liu X, Liu X, Shi Q, Fan X, Qi K. Association of telomere length and telomerase methylation with n-3 fatty acids in preschool children with obesity. BMC pediatrics. 2021;21(1):1-8.
  14. Cassidy A, De Vivo I, Liu Y, Han J, Prescott J, Hunter DJ, et al. Associations between diet, lifestyle factors, and telomere length in women. The American journal of clinical nutrition. 2010;91(5):1273-80.
  15. Chen J, Wei Y, Chen X, Jiao J, Zhang Y. Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis. Oncotarget. 2017;8(5):7301.
  16. Hoseinzade I, Abdi A, Abbassi Daloii A. Protective Effect of Aerobic Training and Royal Jelly on Cellular senescence Markers of Cardiomyocytes in Obese Rats. Journal of Sport and Exercise Physiology. 2022;15(3):91-101. [In Persian]
  17. Mostafavian M, Abdi A, Mehrabani J, Barari A. Effect of Eight Weeks of Aerobic Progressive Training with Capsaicin on changes in PGC-1α and UPC-1 Expression in Visceral Adipose Tissue of Obese Rats With Diet. Complementary Medicine Journal. 2020;10(2):106-17. [In Persian]
  18. Ji N, Luan J, Hu F, Zhao Y, Lv B, Wang W, et al. Aerobic exercise‑stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney. Experimental and therapeutic medicine. 2018;16(4):3511-7.
  19. de Andrade AM, Fernandes MdC, de Fraga LS, Porawski M, Giovenardi M, Guedes RP. Omega-3 fatty acids revert high-fat diet-induced neuroinflammation but not recognition memory impairment in rats. Metabolic Brain Disease. 2017;32(6):1871-81.
  20. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.
  21. Kazemipour M, Matinhomaee H, Farzanegi P. The effect of aerobic exercise with pistachio skin extract on the expression of IL-6, IL-1 and TNF-α in heart tissue of obese rats. Journal of Sport and Exercise Physiology. 2023;15(4/93):102. [In Persian]
  22. Grun LK, da Rosa Teixeira Jr N, von Mengden L, De Bastiani MA, Parisi MM, Bortolin R, et al. TRF1 as a major contributor for telomeres' shortening in the context of obesity. Free Radical Biology and Medicine. 2018;129:286-95.
  23. Njajou OT, Cawthon RM, Blackburn EH, Harris TB, Li R, Sanders JL, et al. Shorter telomeres are associated with obesity and weight gain in the elderly. International journal of obesity. 2012;36(9):1176-9.
  24. Uysal F, Kosebent EG, Toru HS, Ozturk S. Decreased expression of TERT and telomeric proteins as human ovaries age may cause telomere shortening. Journal of Assisted Reproduction and Genetics. 2021;38(2):429-41.
  25. Burchfield JG, Kebede MA, Meoli CC, Stöckli J, Whitworth PT, Wright AL, et al. High dietary fat and sucrose result in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. Journal of biological chemistry. 2018;293(15):5731-45.
  26. Semeraro MD, Almer G, Kaiser M, Zelzer S, Meinitzer A, Scharnagl H, et al. The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats. European Journal of Nutrition. 2022:1-14.
  27. Khodadoost M, Shakeryan S, Arjmand S, Nikbakht M. The Effect of High and Low-Intensity Interval Training on TRF1 and TRF2 Gene Expression in Slow and Fast-Twitch Skeletal Muscles of C57BL/6 Mice: An Experimental Study. Journal of Rafsanjan University of Medical Sciences. 2022;21(1):49-70. [In Persian]
  28. Werner C, Hanhoun M, Widmann T, Kazakov A, Semenov A, Pöss J, et al. Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. Journal of the American College of Cardiology. 2008;52(6):470-82.
  29. Mandal S, Denham MM, Spencer SJ, Denham J. Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses. Pflügers Archiv-European Journal of Physiology. 2022;474(11):1159-69.
  30. Werner CM, Hecksteden A, Morsch A, Zundler J, Wegmann M, Kratzsch J, et al. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study. European heart journal. 2019;40(1):34-46.
  31. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. The EMBO journal. 2003;22(1):131-9.
  32. Oh H, Taffet GE, Youker KA, Entman ML, Overbeek PA, Michael LH, et al. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proceedings of the National Academy of Sciences. 2001;98(18):10308-13.
  33. Ludlow AT, Lima LC, Wang J, Hanson ED, Guth LM, Spangenburg EE, et al. Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK. Journal of applied physiology. 2012;113(11):1737-46.
  34. Chang X, Dorajoo R, Sun Y, Wang L, Ong CN, Liu J, et al. Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population. Nutrition journal. 2020;19(1):1-9.
  35. Varela-Lopez A, Pérez-López MP, Ramirez-Tortosa CL, Battino M, Granados-Principal S, del Carmen Ramirez-Tortosa M, et al. Gene pathways associated with mitochondrial function, oxidative stress and telomere length are differentially expressed in the liver of rats fed lifelong on virgin olive, sunflower or fish oils. The Journal of Nutritional Biochemistry. 2018;52:36-44.
  36. Wu L, Fidan K, Um J-Y, Ahn KS. Telomerase: Key regulator of inflammation and cancer. Pharmacological Research. 2020;155:104726.
  37. Petrillo S, Pelosi L, Piemonte F, Travaglini L, Forcina L, Catteruccia M, et al. Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway. Human Molecular Genetics. 2017;26(14):2781-90.
  38. Ogłuszka M, Te Pas MF, Poławska E, Nawrocka A, Stepanow K, Pierzchała M. Omega-3 alpha-linolenic fatty acid affects the level of telomere binding protein TRF1 in porcine skeletal muscle. Animals. 2020;10(6):1090.
  39. Flor-Alemany M, Acosta-Manzano P, Migueles JH, Varela-López A, Baena-García L, Quiles JL, et al. Influence of an exercise intervention plus an optimal Mediterranean diet adherence during pregnancy on the telomere length of the placenta. The GESTAFIT project. Placenta. 2023;136:42-45.
  40. Shirkhani Y, Peeri M, Azarbayjani MA, Matinhomaee H. Effect of Resistance Exercise and Vitamin C Intake on Expression of Telomerase Reverse Transcriptase and Telomere Repeat Binding Factor-2 Genes and the Diameter and Number of Myofibrils in Old Rats. complementary Medicine Journal. 2021;10(4):396-409. [In Persian]

 

  • تاریخ دریافت: 01 اسفند 1401
  • تاریخ بازنگری: 21 فروردین 1402
  • تاریخ پذیرش: 20 اردیبهشت 1402
  • تاریخ اولین انتشار: 14 مرداد 1402
  • تاریخ انتشار: 01 آذر 1402