اثرات هشت هفته تمرین هوازی و رزوراترول بر بیان ژن‌های دخیل در ترموژنز و پروفایل لیپیدی در موش‌های نر نژاد C57BL/6

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

نویسنده

گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه کاشان، کاشان، ایران

چکیده

هدف: هدف مطالعه حاضر بررسی اثر ترکیبی رزوراترول و تمرین هوازی بر بیان ژن­های درگیر در ترموژنز و پروفایل لیپیدی در بافت چربی زیرپوستی موش­های نژاد C57BL/6 بود. روش شناسی: 32 موش نر با میانگین وزنی 4±16 گرم به طور تصادفی به چهار گروه (تعداد = 8) تقسیم شدند. 1. رزوراترول (Res)، 2. کنترل (Control)، 3. تمرین هوازی (Exe)، 4. تمرین هوازی+رزوراترول(Res+Exe). موش­ها رزوراترول را به مدت هشت هفته، پنج مرتبه/هفته، از طریق گاواژ دریافت کردند. موش­های تمرین کرده به مدت هشت هفته، پنج جلسه/هفته با میانگین شدت 50-65 درصد حداکثر اکسیژن مصرفی تحت تمرین بدنی بر روی نوارگردان قرار گرفتند. پس از اتمام پروتکل پژوهش و 24 ساعت پس از آخرین جلسه تمرین، بافت چربی زیرپوستی استخراج و بیان ژن­ها (PGC1a، FNDC5، UCP1، PRDM16 و (SIRT1 در بافت چربی با استفاده از تکنیک Real-time PCR سنجش شد. همچنین میزان پروفایل چربی (تری گلیسیرید، کلسترول تام، HDL و LDL) ارزیابی شد. یافته ­ها: نتایج نشان داد که سطوح FNDC5، SIRT1 و UCP1 در بافت چربی موش­های گروه Res بالاتر از گروه کنترل بود. همچنین بیان PGC1α، FNDC5، UCP1، PRDM16 و SIRT1 در بافت چربی موش­های Exe بالاتر از گروه کنترل بود. نشانگرهای ترموژنز و ژن­های دخیل در قهوه ای شدن بافت چربی در گروه Res+Exe نسبت به گروه Res و Exe به طور معناداری بالاتر بود. میزان HDL در گروه Res+Exe نسبت به گروه کنترل بالاتر و سطوح LDL، تری گلیسرید و کلسترول تام در گروه Res+Exe نسبت به گروه کنترل پایین­تر بود. نتیجه گیری: تمرین هوازی و رزوراترول اثر هم­افزایی قابل توجهی بر افزایش ترموژنز و افزایش بیان UCP1، PRDM16، PGC1α،SIRT1  و FNDC5 نسبت به گروه تمرین و رزوراترول به تنهایی دارد. افزایش بیان FNDC5 در بافت چربی زیرجلدی که به دنبال مداخله تمرین هوازی و رزوراترول ایجاد می­گردد، توسط SIRT1 تعدیل می­شود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of eight weeks of aerobic exercise and resveratrol on expression of genes involved in thermogenesis and lipid profile in male C57BL/6 mice

نویسنده [English]

  • Fatemeh Kazeminasab
Department of Physical Education and Sport Sciences, Faculty of Human Sciences, University of Kashan, Kashan, Iran
چکیده [English]

Aim: The aim of this study was to evaluate the combined effect of resveratrol and aerobic exercise on the expression of genes involved in thermogenesis and lipid profile in the subcutaneous adipose tissue of C57BL/6 mice. Methods: Thirty-two male mice with a mean weight of 16±4 g were randomly divided into four groups (n=8).  1. Resveratrol (Res), 2. Control, 3. Aerobic exercise (Exe), 4. Resveratrol+Aerobic exercise (Res+Exe). The mice received resveratrol by gavage five times/week for eight weeks. The exercised mice trained on a treadmill for eight weeks, five sessions/week with an average intensity of 65-50% of maximum oxygen consumption (Vo2max). Adipose tissue was extracted after completing the research protocol and 24 hours after the last training session, subcutaneous adipose tissue was extracted and the expression of genes (PGC1a, FNDC5, UCP1, PRDM16, and SIRT1) in adipose tissue was measured using Real-time PCR. Results:  The results showed that the levels of FNDC5, SIRT1, and UCP1 in the adipose tissue of Res mice were higher than the control group.  Also, the expression of PGC1α, FNDC5, UCP1, PRDM16, and SIRT1 in the adipose tissue of Exe mice was higher than the control group. The markers of thermogenesis and genes involved in adipose tissue browning were significantly in the Res+Exe group higher than the Res and Exe groups.  The levels of HDL in the Res+Exe group were higher than the control group and the levels of LDL, triglyceride and total cholesterol were lower in the Res+Exe group than the control group. Conclusions:  Aerobic exercise and resveratrol have a significant synergistic effect on increased thermogenesis and increased expression of UCP1, PRDM16, PGC1α, SIRT1, and FNDC5 compared to Exe and Res group alone.  Increased expression of FNDC5 in subcutaneous adipose tissue following modification of aerobic exercise and resveratrol is modulated by SIRT1.

کلیدواژه‌ها [English]

  • Resveratrol
  • Aerobic exercise
  • Thermogenesis
  • Sirtuin 1 (SIRT1)
  • Fibronectin type III domain-containing protein 5 (FNDC5)

   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

1. Santos SHS, Andrade JMO. Angiotensin 1–7: A peptide for preventing and treating metabolic syndrome. Peptides. 2014;59:34-41.
2. Baglioni S, Cantini G, Poli G, Francalanci M, Squecco R, Di Franco A, et al. Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell. PLoS one. 2012;7(5):e36569.
3. Andrade JMO, Frade ACM, Guimaraes JB, Freitas KM, Lopes MTP, Guimarães ALS, et al. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. European journal of nutrition. 2014;53(7):1503-10.
4. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8.
5. Castillo-Quan JI. From white to brown fat through the PGC-1α-dependent myokine irisin: implications for diabetes and obesity. Disease models & mechanisms. 2012;5(3):293-5.
6. Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Crujeiras AB, et al. FNDC5/irisin is not only a myokine but also an adipokine. PloS one. 2013;8(4):e60563.
7. Khalafi M, Shabkhiz F, Azali Alamdari K, Bakhtiyari A. irisin response to two types of exercise training in type 2 diabetic male rats. Journal of Arak University of Medical Sciences. 2016;19(6):37-45. [In Persian]
8. Stanford KI, Goodyear LJ. Exercise regulation of adipose tissue. Adipocyte. 2016;5(2):153-62.
9. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-42.
10. Olas B, Wachowicz B, Saluk-Juszczak J, Zieliński T, Kaca W, Buczyński A. Antioxidant activity of resveratrol in endotoxin-stimulated blood platelets. Cell biology and toxicology. 2001;17(2):117-25.
11. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. Journal of Biological Chemistry. 2005;280(17):17187-95.
12. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nature reviews Molecular cell biology. 2012;13(4):225-38.
13. Satoh A, Stein L, Imai S. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Histone Deacetylases: the Biology and Clinical Implication. 2011:125-62.
14. Huang Y, Lu J, Zhan L, Wang M, Shi R, Yuan X, et al. Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism. Journal of Biological Chemistry. 2021;297(2).
15. Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Churruca I, Portillo MP. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food chemistry. 2013;141(2):1530-5.
16. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell. 2006;127(6):1109-22.
17. Kazeminasab F, Marandi SM, Ghaedi K, Safaeinejad Z, Esfarjani F, Nasr-Esfahani MH. A comparative study on the effects of high-fat diet and endurance training on the PGC-1α-FNDC5/irisin pathway in obese and nonobese male C57BL/6 mice. Applied physiology, nutrition, and metabolism. 2018;43(7):651-62.
18. Powers SK, Criswell D, Lawler J, Martin D, Lieu F-K, Ji LL, et al. Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium. American Journal of Physiology-Heart and Circulatory Physiology. 1993;265(6):H2094-H8.
19. Kazeminasab F, Marandi SM, Shirkhani S, Sheikhanian Poor A, Ghaedi K. The Effect of 8 Weeks Aerobic Exercise on LXRa, PEPCK, and G6PC2 mRNA in Obese Prediabetic Mice. Sport Physiology. 2020;12(48):17-38. [In Persian]
20. Um J-H, Park S-J, Kang H, Yang S, Foretz M, McBurney MW, et al. AMP-activated protein kinase–deficient mice are resistant to the metabolic effects of resveratrol. Diabetes. 2010;59(3):554-63.
21. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. Journal of neuroinflammation. 2017;14(1):1-10.
22. Andrade JMO, Barcala-Jorge AS, Batista-Jorge GC, Paraíso AF, de Freitas KM, de Farias Lelis D, et al. Effect of resveratrol on expression of genes involved thermogenesis in mice and humans. Biomedicine & Pharmacotherapy. 2019;112:108634.
23. Shirkhani S, Marandi SM, Kazeminasab F, Esmaeili M, Ghaedi K, Esfarjani F, et al. Comparative studies on the effects of high-fat diet, endurance training and obesity on Ucp1 expression in male C57BL/6 mice. Gene. 2018;676:16-21.
24. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, et al. Evidence against a beneficial effect of irisin in humans. PloS one. 2013;8(9):e73680.
25. Jimenez-Gomez Y, Mattison JA, Pearson KJ, Martin-Montalvo A, Palacios HH, Sossong AM, et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell metabolism. 2013;18(4):533-45.
26. Fiori JL, Shin Y-K, Kim W, Krzysik-Walker SM, González-Mariscal I, Carlson OD, et al. Resveratrol prevents β-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet. Diabetes. 2013;62(10):3500-13.
27. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, et al. Substrate-specific activation of sirtuins by resveratrol. Journal of Biological Chemistry. 2005;280(17):17038-45.
28. Zheng X, Ai H, Yuan S, Cao H, Liang H, Weng J, et al. Effect of SIRT1 deficiency on function of brown adipose tissue in obese mice. Zhonghua yi xue za zhi. 2016;96(23):1859-62.
29. Wang S, Liang X, Yang Q, Fu X, Zhu M, Rodgers B, et al. Resveratrol enhances brown adipocyte formation and function by activating AMP‐activated protein kinase (AMPK) α1 in mice fed high‐fat diet. Molecular nutrition & food research. 2017;61(4):1600746.
30. Jørgensen SB, Richter EA, Wojtaszewski JF. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise. The Journal of physiology. 2006;574(1):17-31.
31. Marcinko K, Steinberg GR. The role of AMPK in controlling metabolism and mitochondrial biogenesis during exercise. Experimental physiology. 2014;99(12):1581-5.
32. Richter EA, Ruderman NB. AMPK and the biochemistry of exercise: implications for human health and disease. Biochemical Journal. 2009;418(2):261-75.
33. Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012;150(3):620-32.