The Effect of Aerobic Exercise and Omega-3 on Inflammatory and Oxidative Stress in the Heart Tissue of Elderly HFD Rats

Document Type : Original Article (s)

Authors

1 PhD Candidate, Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

2 Associate Professor, Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

Abstract

Background: Aging and obesity are associated with systemic inflammation and increased oxidative stress. Aerobic exercise and omega-3 play an important role in modulating oxidative stress and inflammation. The purpose of this study is to investigate the effect of aerobic exercise and omega-3 on inflammatory and oxidative stress in the heart tissue of elderly rats fed a high-fat diet.
Methods: In this experimental study, 40 male Wistar rats (mean weight 311.32 ± 26.95) were divided into
5 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). The supplement groups received 1 g of Omega3 (per kg of body weight) orally during the intervention period.An aerobic exercise program including running on a treadmill with an intensity of 50-60% maximal oxygen consumption (VO2max), was performed 5 days a week for eight weeks. The tissue concentration of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) was measured by ELISA method using special kits for rats.
Findings: Significant decrease were seen in TNF-α, IL-6, and NF-κB gene expression levels in HFDT, HFDω3, and HFDTω3. This decrease was also observed in the HFDTω3 group compared with the HFDT group and HFDω3 group. Also, significant decrease was observed in MDA values. Findings showed significant increase in Nuclear factor erythroid 2-related factor 2, SOD, GPX, and CAT in experimental groups compared with HFD.
Conclusion: Combining aerobic exercise with omega-3 may ameliorate HFD-induced heart damage in elderly rats by reducing inflammation and oxidative stress.

Keywords

Main Subjects


  1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation 2021; 143(8): e254-743.
  2. Pérez LM, Pareja‐Galeano H, Sanchis‐Gomar F, Emanuele E, Lucia A, Gálvez BG. ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J Physiol 2016; 594(12): 3187-207.
  3. Fiordelisi A, Iaccarino G, Morisco C, Coscioni E, Sorriento D. NFkappaB is a key player in the crosstalk between inflammation and cardiovascular diseases. Int J Mol Sci 2019; 20(7): 1599.
  4. Csiszar A, Wang M, Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-κB. J Appl Physiol (1985) 2008; 105(4): 1333-41.
  5. Hamid T, Guo SZ, Kingery JR, Xiang X, Dawn B,
    Prabhu SD. Cardiomyocyte NF-κB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure. Cardiovasc Res 2011; 89(1): 129-38.
  6. Zhu B, Zhang L, Liang C, Liu B, Pan X, Wang Y, et al. Stem cell-derived exosomes prevent aging-induced cardiac dysfunction through a novel exosome/lncRNA MALAT1/NF-κB/TNF-α signaling pathway. Oxid Med Cell Longev 2019; 2019: 9739258.
  7. Rizvi F, Preston CC, Emelyanova L, Yousufuddin M, Viqar M, Dakwar O, et al. Effects of aging on cardiac oxidative stress and transcriptional changes in pathways of reactive oxygen species generation and clearance. J Am Heart Assoc 2021; 10(16): e019948.
  8. Zhang L, Yousefzadeh MJ, Suh Y, Niedernhofer LJ, Robbins PD. Signal transduction, ageing and disease. Subcell Biochem 2019; 91: 227-47.
  9. Tonelli C, Chio IIC, Tuveson DA. Transcriptional
    regulation by Nrf2. Antioxid Redox Signal 2018; 29(17): 1727-45.
  10. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats: the role of transcriptional factor Nrf2 and MAPK signaling pathway. Biogerontology 2007; 8(2): 71-80.
  11. Gounder SS, Kannan S, Devadoss D, Miller CJ, Whitehead KS, Odelberg SJ, et al. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training. PLoS One 2012; 7(9): e45697.
  12. Liu HW, Chang SJ. Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α Axis to attenuate muscle loss in diabetic db/db mice. Front Physiol 2018; 9: 636.
  13. Hoseinzadeh I, Abdi A, Abbassi Daloii A. Protective effect of aerobic training and royal jelly on oxidative stress in cardiomyocytes in obese rats [in Persian]. J Mazandaran Uni Med Sci 2022; 31(206): 30-42.
  14. Amos D, Cook C, Santanam N. Omega 3 rich diet modulates energy metabolism via GPR120-Nrf2 crosstalk in a novel antioxidant mouse model. Biochim Biophys Acta Mol Cell Biol Lipids 2019; 1864(4): 466-88.
  15. Davinelli S, Medoro A, Intrieri M, Saso L, Scapagnini G, Kang JX. Targeting NRF2-KEAP1 axis by Omega-3 fatty acids and their derivatives: Emerging opportunities against aging and diseases. Free Radic Biol Med 2022; 193(Pt 2): 736-50.
  16. 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 [in Persian]. Complement Med J 2020; 10(2): 106-17.
  17. 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. Exp Ther Med 2018; 16(4): 3511-7.
  18. de Andrade AM, da Cruz Fernandes M, 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. Metab Brain Dis 2017; 32(6): 1871-81.
  19. Bondia-Pons I, Ryan L, Martinez JA. Oxidative stress and inflammation interactions in human obesity.
    J Physiol Biochem 2012; 68(4): 701-11.
  20. Meng SJ, Yu LJ. Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 2010; 11(4): 1509-26.
  21. Seo DY, Hwang BG. Effects of exercise training on the biochemical pathways associated with sarcopenia. Phys Act Nutr 2020; 24(3): 32-8.
  22. Li Y, Shi B, Dong F, Zhu X, Liu B, Liu Y. Effects of inflammatory responses, apoptosis, and STAT3/NF-κB-and Nrf2-mediated oxidative stress on benign prostatic hyperplasia induced by a high-fat diet. Aging (Albany NY) 2019; 11(15): 5570-78.
  23. Davaran M, Abdi A, Mehrabani J, Daloii AA. Response of cardiac tissue oxidative stress after aerobic exercise and capsaicin administrations in rats fed high-fat diet. Zahedan J Res Med Sci 2022; 24(1): e107861.
  24. Rami M, Azimpour M, Khoramipour K. The effect of 8 weeks of high intensity interval training on the levels of Wnt and NF-κB proteins in the heart tissue of male wistar rats with type 2 diabetes [in Persian]. J Sport Exe Physiol 2022; 15(4): 19-30.
  25. Wang L, Lavier J, Hua W, Wang Y, Gong L, Wei H, et al. High-intensity interval training and moderate-intensity continuous training attenuate oxidative damage and promote myokine response in the skeletal muscle of ApoE KO mice on high-fat diet. Antioxidants (Basel) 2021; 10(7): 992.
  26. Golpour P, Nourbakhsh M, Mazaherioun M, Janani L, Nourbakhsh M, Yaghmaei P. Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial. Diabetes Res Clin Pract 2020; 162: 108120.
  27. Marion-Letellier R, Savoye G, Ghosh S. Fatty acids, eicosanoids and PPAR gamma. Eur J Pharmacol 2016; 785: 44-9.
  28. Fang IM, Yang CH, Yang CM. Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant protein‐1 expression via PPARγ and nuclear factor‐κB pathway in retinal pigment epithelial cells. Mol Nutr Food Res 2014; 58(10): 2053-65.
  29. Huang CH, Hou YC, Yeh CL, Yeh SL. A soybean and fish oil mixture with different n-6/n-3 PUFA ratios modulates the inflammatory reaction in mice with dextran sulfate sodium-induced acute colitis. Clin Nutr 2015; 34(5): 1018-24.
  30. Natto ZS, Yaghmoor W, Alshaeri HK, Van Dyke TE. Omega-3 fatty acids effects on inflammatory biomarkers and lipid profiles among diabetic and cardiovascular disease patients: a systematic review and meta-analysis. Sci Rep 2019; 9(1): 18867.
  31. Patterson III WL, Georgel PT. Breaking the cycle: the role of omega-3 polyunsaturated fatty acids in inflammation-driven cancers. Biochem Cell Biol 2014; 92(5): 321-8.
  32. Trebble T, Arden NK, Stroud MA, Wootton SA, Burdge GC, Miles EA, et al. Inhibition of tumour necrosis factor-α and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Br J Nutr 2003; 90(2): 405-12.
  33. Von Schacky C, Kiefl R, Jendraschak E, Kaminski WE. n-3 fatty acids and cysteinyl-leukotriene formation in humans in vitro, ex vivo, and in vivo. J Lab Clin Med 1993; 121(2): 302-9.
  34. Volpato M, Ingram N, Perry SL, Spencer J, Race AD, Marshall C, et al. Cyclooxygenase activity mediates colorectal cancer cell resistance to the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Chemother Pharmacol 2021; 87(2): 173-84.
  35. Jala VR, Bodduluri SR, Satpathy SR, Chheda Z, Sharma RK, Haribabu B. The yin and yang of leukotriene B4 mediated inflammation in cancer.
    Semin Immunol 2017; 33(1): 58-64.
  36. Yang M, Bair JA, Hodges RR, Serhan CN, Dartt DA. Resolvin E1 reduces leukotriene B4-induced intracellular calcium increase and mucin secretion in rat conjunctival goblet cells. Am J Pathol 2020; 190(9): 1823-32.
  37. Lee TH, Hoover RL, Williams JD, Sperling RI, Ravalese III J, Spur BW, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985; 312(19): 1217-24.
  38. Veras ASC, Gomes RL, Almeida Tavares ME, Giometti IC, Cardoso APMM, da Costa Aguiar Alves B, et al. Supplementation of polyunsaturated fatty acids (PUFAs) and aerobic exercise improve functioning, morphology, and redox balance in prostate obese rats. Sci Rep 2021; 11(1): 6282.
  39. Saedmocheshi S, Saed L, Saiedi A, Vahabzade Z. Effect of aerobic exercise training along with omega-3 supplementation on CRP and IL-6 in obese older women [in Persian]. Med J Tabriz Uni Med Sci Health Ser 2019; 41(4): 49-55.
  40. Montazer S, Gholami M, Azarbayjani MA, Abed Natanzi H. Effects of aerobic training and omega-3 supplementation on the levels of CRP, MDA and lipid profile in overweight and obese women. J Bas Res Med Sci 2021; 8(4): 60-70.