Document Type : Research Paper

Authors

1 Ph.D. of Sport Biochemistry and Metabolism, Azad University, Central Tehran Branch

2 Professor of Sport Physiology, Azad University, Central Tehran Branch

3 Associate Professor of Biochemistry, Shahid Beheshti University of Medical Sciences

4 M. Sc. of Sport Physiology, Shahid Beheshti University of Medical Sciences

5 M. Sc. of Sport Physiology, Razi University

Abstract

The purpose of this study was to determine the effects of resveratrol supplementation and Aerobic training on protein levels of SIRT-1, PGC-1α and UCP-1 soleus muscle and Ingoinal abdominal subcutaneous adipose tissue in adult male Wistar rats. In this study, 32 male rat (w=260+10gr, 8 weeks) divided into 4(n=8) groups: control(C), aerobic training (T), complement-training (T-R) and supplements(S) randomly. Training groups exercised for 12 weeks (5 sessions a week, each session 45 minutes on a treadmill. ELISA (sandwich double) was used to measure tissue protein UCP-1, SIRT1, PGC-1α. ANOVA test used for data analysis and statistical significance (P≤0.05) were considered. Increased SIRT1 and PGC-1α protein changes in T-R and S groups in muscle tissue and subcutaneous white adipose tissue, respectively (P≤0.001) and (P≤0.05). Showed that the protein UCP-1 is also a significant increase in subcutaneous white adipose tissue after workouts (P≤0.001). According to the results probably resveratrol supplementation with aerobic physical activity a stronger impact on increasing the SIRT-1, PGC-1α soleus muscle and inguinal adipose tissue and UCP-1 inguinal adipose tissue to use separately or supplement physical activity resveratrol and white fat and is likely to change subcutaneous white adipose tissue to beige or intermediate phenotype.

Keywords

Main Subjects

1. Shimizu M, Kubota M, Tanaka T. Moriwaki H. Nutraceutical approach for preventing obesity related colorectal and liver carcinogenesis. Int J Mol Sci. 2012; 13:579–95.
2. Dankel SN, Staalesen V, Bjørndal B, Berge RK, Mellgren G, BurriL.Tissue-specific effects of bariatric surgery including mitochondrial function. J Obes. 2011; 13(1): 435245, 2011.
3. Bjørndal B, Burri L, Staalesen V, Skorve J, Berge RK. Differentadipose depots: Their role in the development of metabolic syndrome andmitochondrial response to hypolipidemic agents. J Obes. 2011; 15 pages: 490650.
4. Lagouge M1, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F,et al. Resveratrol improves mitochondrial function and protects against metabolic disease by acti-vating SIRT1 and PGC-1alpha Cell. 2006; 127: 1109-22.
5. Adam Labbé Chantal Garand Victoria C. Cogger Eric R. Paquet Myriam DesbiensDavid G. Le Couteur Michel Lebel et al. Resveratrol improves insulin resistance, hyperglycemia and hepatosteatosis but not hypertriglyceri- demia, inflammation and life span in a mouse model for Werner syndrome. J Gerontol A BiolSci Med Sci. 2011;66: 264–78.
6. Rivera L, Moron R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009; 77: 1053–63.
7. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado de Oliveira, R, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004;429(6993):771–6.
8. Sin TK, Yung BY, Siu PM. Modulation of SIRT1-Foxo1 signaling axis by resveratrol: Implications in skeletal muscle aging and insulin resistance. Cell Physiol Biochem. 2015;35(2):541–52.
9. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010; 285: 8340-51.
10. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, et al. SIRT1 redistribution on chromatin promotes genomic stability but alters geneexpression during aging. Cell. 2008;135(5):907–18.
11. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim S, Mostoslavsky R, et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007; 26: 1913–23.
12. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: Is beige the new brown? GaD 2013;27(3):234-50.
13. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000;289(5487), 2126–28.
14. Polyzos SA, Kountouras J, Shields K, Mantzoros CS. Irisin: A renaissance in metabolism? Metabolism. 2013;62(8):1037-44.
15. Chang JS, Fernand V, Zhang Y, Shin J, Jun HJ, Joshi Y, et al. NT-PGC-1alpha protein is sufficient to link beta3-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis. J Biol Chem. 2012; 287:9100–11.
16. Handschin C, Spiegelman BM: The role of exercise and PGC-1Αalpha in inflammation and chronic disease. Nature. 2008; 454: 463–9.
17. Um JH1, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH., et al. AMP-activated protein kinase-deficient mice are resistant to the metabolic effect of resveratrol. Diabetes. 2010; 59: 554-63.
18. Waldén TB. Regulatory factors that reveal three distinct adipocytes: The brown, the white and the brite (Doctoal dissertation). Sweden: The Wenner-Gren Institute, Stockholm University; 2010. p. 89.
19. Reisi H, Rajabi H, Ghaedi J, Marandi K, Asady samani Z, Kazemi Nasab F. Effect of eight weeks’ resistance training on plasma irisin protein level and muscle FNDC5 and adipose tissue UCP1 genes expression in male rats. JSP. 2016; 7(28): 117-30. (In Persian).
20. Sluse FE, Jarmuszkiewicz W, Navet R, Douette P, Mathy G, Sluse-Goffart CM. Mitochondrial UCPs: New insights into regulation and impact. C(BBA)-Bioenergetics. 2006; 1757(5-6): 480-5.
21. Jeong JH, Lee YR, Park HG, Lee WL.The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice. J Exerc Nutrition Biochem.2015;19(2): 65–72.
22. Granneman JG, Li P, Zhu Z, Lu Y. Metabolic and cellular plasticity in white adipose tissue I: Effects of beta3-adrenergic receptor activation. Am J PhysiolEndocrinolMetab. 2005; 289: 608–16.
23. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B. Chronic peroxisome proliferator-activated receptor γ(PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP-1-containing adipocytes molecularly distinct from classic brown adipocytes. Journal of Biological Chemistry.2010; 285: 7153–64.
24. Fisher F, Kleiner S, Douris N, Fox E, Mepani R, Verdeguer F, et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. G&D 2012; 26: 271–81.
25. Um JH1, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH. Resveratrol enhanced FOXO3 phosphorylation via synergeticactivation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. Age (Dordr). 2014; 36(5): 9705.
26. Fortunato RS, Ignacio DL, Padron AS, Pecanha R, Marassi MP, Rosenthal D, et al. The effect of acute exercise session on thyroid hormone economy in rats. J Endocrinol. 2008; 198: 347–53.
27. Stanford KL, Middelbeek RJ, Goodyear LJ. Exercise effects on white adipose tissue: Beiging and metabolic adaptations. Diabetes. 2015;64(7):2361–8.
28. Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, et al. The effects of acute and chronic exercise on PGC-1a, irisinand browning of subcutaneous adipose tissue in humans: FEBS Journal. 2014;281(3):739–49.
29. Boström P, Wu J, Jedrychowski MP, KordeA,Ye L, Lo JC, et al. A PGC-1Α-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 48: 463–8.
30. Lin H, Lin C, Ting J, Pai Y, Kuo H, Ho TJ, et al. Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. Age(Dordr). 2014; 36(5), 970-84
31. Lagouge M1, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P,et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1 alpha. Cell. 2006; 127: 1109–22.
32. Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013; 33: 2895–901.
33. Dash, S., Xiao, C., Morgantini, C., Szeto, L. & Lewis, G. F. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler. Thromb. Vasc. Biol. (2013), 33, 2895–901.
34. Fernando Lizcano, Diana Vargas. Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity. IJOE. 2016, Article ID 9542061, 10 pages.
35. Ling Li, Ruping P, Rong L, Bernd N, Anne-Cathleen A,Ying C, et al. Mitochondrial biogenesis and peroxisome proliferator–activated receptor-? Coactivator-1?(PGC-1?) deacetylation by physical activity intact adipocytokine signaling is required. Diabetes. 2011; 60: 157–67.
36. Baur JA. Biochemical effects of SIRT1 activators. Biochim Biophys Acta. 2010; 1804(8): 1626–34.
37. Wu J, Cohen P, Spiegelman B M. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes and Development. 2013;27(3):234-50.
38. Leone TC, Lehman JJ, Finck BN, Schaeffer PJ,Wende AR, Boudina S, et al. PGC-1α deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol. 2005; 3: 101.
39. Pontus B, Jun W, Mark P J, Anisha K, Li Y, James C, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481(7382): 463-8. doi: 10.1038/nature10777
40. Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S.K.,Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., Wright, S.M., Mills, K.D.,Bonni, A., Yankner, B.A., Scully, R., Prolla, T.A., Alt, F.W., Sinclair, D.A.,.SIRT1 redistribution on chromatin promotes genomic stability but alters geneexpression during aging. Cell 2008 135(5), 907–18.
41. Nemoto, S., Fergusson, M.M., and Finkel, T. SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J. Biol. Chem. 2005, 280, 16456-60.
42. Matos RS, Baroncini LAV, Précoma LB, Winter G, Lambach PH, Caron EY, Kaiber F & Précoma DB (2012). Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis. Arq Bras Cardiol 98, 136–42.
43. Picard, F., Kurtev, M., Chung, N., Topark-Ngarm, A., Senawong, T., Machado De Oliveira, R., Leid, M., McBurney, M.W., Guarente, L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004. 429(6993), 771–6.
44. Li P, Zhu Z, Lu Y, Granneman JG. Metabolic and cellular plasticity in white adipose tissue II: Role of peroxisome proliferator-activated receptor-α. Am J Physiol Endocrinol Metab. 2005; 289: 617–26.
45. Matos RS, Baroncini LAV, Précoma LB, Winter G, Lambach PH, Caron EY, et al. Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis. Arq Bras Cardiol. 2012; 98:136–42.
46. Ikeda S, Kawamoto H, Kasaoka K, Hitomi Y, Kizaki T, Sankai Y, et al. Muscle type-specific response of PGC-1 alpha and oxidative enzymes during voluntary wheel running in mouse skeletal muscle. Acta Physiol (Oxf). 2006; 188: 217–23.
47. Matos RS, Baroncini LAV, Précoma LB, Winter G, Lambach PH, Caron EY, Kaiber F & Précoma DB (2012). Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis. Arq Bras Cardiol 98, 136–42.