The Effect of Training and Royal Jelly on the Expression of FoxO3a, MAFbx and AMPK of Cardiomyocytes in Obese Rats

Document Type : Research Paper

Author

Department of Exercise Physiology, Faculty of Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.

Abstract

Introduction: Overweight and obesity increase the risk of cardiovascular diseases. Obesity is also known to contribute to heart muscle atrophy. This study investigates the effects of aerobic exercise and royal jelly (RJ) supplementation on indices of heart tissue atrophy and hypertrophy in rats fed a high-fat diet. Methods: Forty-five male Wistar rats were randomly divided into five groups (n=9 per group): normal diet (ND), high-fat diet (HFD), high-fat diet with training (HFDT), high-fat diet with royal jelly (HFDRJ), and high-fat diet with both training and royal jelly (HFDTRJ). The supplement groups received 100 mg of royal jelly per kg of body weight orally every day. The exercise program involved running on a treadmill at an intensity of 50-60% of VO2max, performed five days a week for eight weeks. Data were analyzed using one-way ANOVA and Tukey's post hoc test with a significance level of p<0.05. Results: In the HFD group, the expression of FoxO3a and MAFbx was significantly increased, while AMPK expression was decreased compared to the ND group (P=0.000). There was a significant decrease in FoxO3a and MAFbx expression in the HFDT (P=0.033 and P=0.027), HFDRJ (P=0.049 and P=0.041), and HFDTRJ (P=0.000 and P=0.000) groups compared to the HFD group. Additionally, the HFDTRJ group showed significant reductions in FoxO3a and MAFbx compared to the HFDT (P=0.045 and P=0.041) and HFDRJ (P=0.030 and P=0.027) groups. A significant increase in AMPK expression was observed in the HFDT (P=0.002), HFDRJ (P=0.007), and HFDTRJ (P=0.000) groups compared to the HFD group. Furthermore, the HFDTRJ group exhibited higher AMPK expression compared to the HFDT (P=0.048) and HFDRJ (P=0.015) groups. Conclusions: Aerobic training, with or without the intake of royal jelly, leads to a reduction in the expression of FoxO3a and MAFbx and an increase in AMPK. These changes may result in decreased atrophy indices and enhanced hypertrophy of cardiomyocytes in rats fed a high-fat diet.

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References

  1. Tutor AW, Lavie CJ, Kachur S, Milani RV, Ventura HO. Updates on obesity and the obesity paradox in cardiovascular diseases. Progress in Cardiovascular Diseases. 2023;78:2-10.
  2. Baek K, Kang J, Lee J, Kim M, Baek J-H. The time point-specific effect of beta-adrenergic blockade in attenuating high fat diet-induced obesity and bone loss. Calcified Tissue International. 2018;103:217-26.
  3. Perl A. mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Annals of the new York Academy of Sciences. 2015;1346(1):33-44.
  4. Chen K, Gao P, Li Z, Dai A, Yang M, Chen S, et al. Forkhead Box O signaling pathway in skeletal muscle atrophy. The American Journal of Pathology. 2022;192(12):1648-57.
  5. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117(3):399-412.
  6. Relling DP, Esberg LB, Fang CX, Johnson WT, Murphy EJ, Carlson EC, et al. High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis. Journal of Hypertension. 2006;24(3):549-61.
  7. Kandula V, Kosuru R, Li H, Yan D, Zhu Q, Lian Q, et al. Forkhead box transcription factor 1: role in the pathogenesis of diabetic cardiomyopathy. Cardiovascular Diabetology. 2016;15:1-12.
  8. Torabi Palat Kaleh G, Abdi A, Abbassi Daloii A. The Effect of Aerobic Exercise and Omega-3 on Atrophy Indices in the Cardiomyocytes of Elderly HFD Rats. Metabolism and Exercise. 2022;12(1):73-87.
  9. Lu C, Gao C, Wei J, Dong D, Sun M. SIRT1-FOXOs signaling pathway: A potential target for attenuating cardiomyopathy. Cellular Signalling. 2024:111409.
  10. Dey G, Bharti R, Dhanarajan G, Das S, Dey KK, Kumar BP, et al. Marine lipopeptide Iturin A inhibits Akt mediated GSK3β and FoxO3a signaling and triggers apoptosis in breast cancer. Scientific Reports. 2015;5(1):10316.
  11. Cho C, Ji M, Cho E, Yi S, Kim JG, Lee S. Chronic voluntary wheel running exercise ameliorates metabolic dysfunction via PGC-1α expression independently of FNDC5/irisin pathway in high fat diet-induced obese mice. The Journal of Physiological Sciences. 2023;73(1):6.
  12. Hood DA, Irrcher I, Ljubicic V, Joseph A-M. Coordination of metabolic plasticity in skeletal muscle. Journal of Experimental Biology. 2006;209(12):2265-75.
  13. Liu H-W, Chang S-J. Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α Axis to attenuate muscle loss in diabetic db/db mice. Frontiers in Physiology. 2018;9:636.
  14. Niu K, Guo H, Guo Y, Ebihara S, Asada M, Ohrui T, et al. Royal jelly prevents the progression of sarcopenia in aged mice in vivo and in vitro. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2013;68(12):1482-92.
  15. Takahashi Y, Hijikata K, Seike K, Nakano S, Banjo M, Sato Y, et al. Effects of royal jelly administration on endurance training-induced mitochondrial adaptations in skeletal muscle. Nutrients. 2018;10(11):1735.
  16. Meng G, Wang H, Pei Y, Li Y, Wu H, Song Y, et al. Effects of protease-treated royal jelly on muscle strength in elderly nursing home residents: A randomized, double-blind, placebo-controlled, dose-response study. Scientific Reports. 2017;7(1):11416.
  17. Okumura N, Toda T, Ozawa Y, Watanabe K, Ikuta T, Tatefuji T, et al. Royal jelly delays motor functional impairment during aging in genetically heterogeneous male mice. Nutrients. 2018;10(9):1191.
  18. Watadani R, Kotoh J, Sasaki D, Someya A, Matsumoto K, Maeda A. 10-Hydroxy-2-decenoic acid, a natural product, improves hyperglycemia and insulin resistance in obese/diabetic KK-Ay mice, but does not prevent obesity. Journal of Veterinary Medical Science. 2017;79(9):1596-602.
  19. Fathi R, Ebrahimi M, Khenar Sanami S. Effects of high fat diet and high intensity aerobic training on interleukin 6 plasma levels in rats. Pathobiology Research. 2015;18(3):109-16.
  20. Rocha-Rodrigues S, Rodríguez A, Gouveia AM, Gonçalves IO, Becerril S, Ramírez B, et al. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sciences. 2016;165:100-8.
  21. Mesri Alamdari N, Irandoost P, Roshanravan N, Vafa M, Asghari Jafarabadi M, Alipour S, et al. Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity. Nutrition & Metabolism. 2020;17:1-13.
  22. Hasan MM, Shalaby SM, El‐Gendy J, Abdelghany EM. Beneficial effects of metformin on muscle atrophy induced by obesity in rats. Journal of Cellular Biochemistry. 2019;120(4):5677-86.
  23. Abrigo J, Rivera JC, Aravena J, Cabrera D, Simon F, Ezquer F, et al. High fat diet‐induced skeletal muscle wasting is decreased by mesenchymal stem cells administration: implications on oxidative stress, ubiquitin proteasome pathway activation, and myonuclear apoptosis. Oxidative Medicine and Cellular longevity. 2016;2016(1):9047821.
  24. Cao G, Lin M, Gu W, Su Z, Duan Y, Song W, et al. The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts. Life Sciences. 2023;328:121877.
  25. Baracos V, Arribas L. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Annals of Oncology. 2018;29:ii1-9.
  26. Roy B, Curtis ME, Fears LS, Nahashon SN, Fentress HM. Molecular mechanisms of obesity-induced osteoporosis and muscle atrophy. Frontiers in Physiology. 2016;7:439.
  27. Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. The FEBS Journal. 2013;280(17):4294-314.
  28. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303(5666):2011-5.
  29. Esmailee B, Abdi A, Abbassi Daloii A, Farzanegi P. The effect of aerobic exercise along with resveratrol supplementation on myocardial AMPK and MAFbx gene expression of diabetic rats. Journal of Birjand University of Medical Sciences. 2020;27(2):150-60.
  30. Esmailee B, Abdi A, Abbassi Daloii A, Farzanegi P. The effect of aerobic exercise along with resveratrol supplementation on myocardial AMPK and MAFbx gene expression of diabetic rats. Journal of Birjand University of Medical Sciences. 2020;27(2):150-60.
  31. Rahimi A, Delfan M, Daneshyar S. The effect of metformin along with high-intensity interval training on gene expression of FoxO1 and Atrogin-1 in type 2 diabetic mice. Journal of Shahrekord University of Medical Sciences. 2023;25(3):124-9.
  32. Aghaei Bahmanbeglou N, Salboukhi R, Sherafati Moghadam M. The Effect of Protein Kinase-B on FOXO Autophagy Family Proteins (FOXO1 and FOXO3a) Following High Intensity Interval Training in the Left Ventricle of the Heart of Diabetic Rats by Streptozotocin and Nicotinamide. Iran J Diabetes Lipid Dis. 2021;21(2):119-28.
  33. Holloway TM, Bloemberg D, da Silva ML, Simpson JA, Quadrilatero J, Spriet LL. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats. PloS one. 2015;10(3):e0121138.
  34. You M, Miao Z, Pan Y, Hu F. Trans-10-hydroxy-2-decenoic acid alleviates LPS-induced blood-brain barrier dysfunction by activating the AMPK/PI3K/AKT pathway. European Journal of Pharmacology. 2019;865:172736.
  35. You M, Miao Z, Tian J, Hu F. Trans-10-hydroxy-2-decenoic acid protects against LPS-induced neuroinflammation through FOXO1-mediated activation of autophagy. European Journal of Nutrition. 2020;59:2875-92.
  36. Zhu Z, Yang C, Iyaswamy A, Krishnamoorthi S, Sreenivasmurthy SG, Liu J, et al. Balancing mTOR signaling and autophagy in the treatment of Parkinson’s disease. International Journal of Molecular Sciences. 2019;20(3):728.
  37. Wang X, Cook LF, Grasso LM, Cao M, Dong Y. Royal jelly-mediated prolongevity and stress resistance in Caenorhabditis elegans is possibly modulated by the interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2015;70(7):827-38.
  38. Milan G, Romanello V, Pescatore F, Armani A, Paik J-H, Frasson L, et al. Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy. Nature Communications. 2015;6(1):6670.

 

Journal of Nutrition,Fasting and Health
Volume 13, Issue 1
March 2025
Pages 69-76

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History

  • Receive Date: 31 August 2024
  • Revise Date: 02 November 2024
  • Accept Date: 03 November 2024

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