Journal of Nutrition,Fasting and Health

Journal of Nutrition,Fasting and Health

Synergistic Effect of High Intensity Interval Training and Atorvastatin in Treatment of NAFLD in Rats Fed High Fat/Fructose Diet

Document Type : Research Paper

Authors
Raouf Moradian 1
Amir Haji Ghasem 1
Saleh Rahmati 2
Lida Moradi 3
1 Department of Physical Education and Sports Sciences, Central Tehran Branch, Islamic Azad University Tehran, Iran
2 Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran.
3 Department of Physical Education and Sports Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
10.22038/jnfh.2024.75313.1467
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease that ranges from steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and liver carcinoma. With the increasing prevalence of NAFLD, there is a growing need for effective prevention and treatment strategies. Stable pharmaceutical compositions containing atorvastatin have been developed to treat hypercholesterolemia and related conditions. In addition, high-intensity interval training (HIIT) can have positive effects on NAFLD. Methods: Twenty-one male Wistar rats were divided into 2 groups: 1) high fat-fructose diet (HFFD) + HIIT, 2) HFFD + HIIT + atorvastatin. The groups received HFFD for 15 weeks to induce NAFLD. Atorvastatin was administrated at the dose of 2 mg/kg/day. The interventions (atorvastatin and HIIT) were done for 8 weeks. Results: Triglyceride (TG), Alanine transaminase (ALT), and aspartate transaminase (AST) were significantly reduced in the HFFD + HIIT + atorvastatin. The groups had no significant difference in weight, low-density lipoprotein (LDL), alkaline phosphatase (ALP), and HDL/LDL ratio. Conclusion: Although atorvastatin along with HIIT reduced aminotransferase, HIIT has benefits in improving lipid profile. Combining atorvastatin and HIIT may offer synergistic benefits in managing NAFLD by targeting both liver enzymes and inflammation.
Keywords
Atorvastatin
High-Fat-Fructose diet
Non-alcoholic fatty liver disease
High intensity interval training
Subjects
  1. McCullough AJ. Update on nonalcoholic fatty liver disease. J Clin Gastroenterol. 2002;34(3):255-62.
  2. Bellentani S. The epidemiology of non-alcoholic fatty liver disease. Liver Int. 2017;37 Suppl 1:81-4.
  3. Eshraghian A, Dabbaghmanesh MH, Eshraghian H, Fattahi MR, Omrani GR. Nonalcoholic fatty liver disease in a cluster of Iranian population: thyroid status and metabolic risk factors. Arch Iran Med. 2013;16(10):584-9.
  4. Lankarani KB, Ghaffarpasand F, Mahmoodi M, Lotfi M, Zamiri N, Heydari ST, et al. Non alcoholic fatty liver disease in southern Iran: a population based study. Hepat Mon. 2013;13(5):e9248.
  5. Eslami Z, Mohammadnajad Panah kandi Y, Norouzi A, Eghbal Moghanlou A, Sheikh arabi M, Kazeminejad V, et al. Changes in blood lipids and enzymatic reactions in response to atorvastatin administration following a high-fat diet in a NAFLD rat model. Medical Laboratory Journal. 2022;16(3):7-13.
  6. Soleimani A, Shakerian S, Ranjbar R. Changes in liver enzymes after the implementation of astrand and rast tests in overweight individuals. Journal of Advances in Medical and Biomedical Research. 2019;27(121):1-7.
  7. Kessler HS, Sisson SB, Short KR. The potential for high-intensity interval training to reduce cardiometabolic disease risk. Sports Med. 2012;42(6):489-509.
  8. Ghasemi E, Afzalpour ME, Zarban A. Effect of a 10 week high intensity interval training supplemented with green tea on lipid profiles and body composition in overweight women. Journal of Birjand University of Medical Sciences. 2016;23(3):198-210.
  9. Houghton D, Thoma C, Hallsworth K, Cassidy S, Hardy T, Burt AD, et al. Exercise Reduces Liver Lipids and Visceral Adiposity in Patients With Nonalcoholic Steatohepatitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2017;15(1):96-102.e3.
  10. Bussau VA, Ferreira LD, Jones TW, Fournier PA. The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes. Diabetes Care. 2006;29(3):601-6.
  11. Mirghani SJ, Seydyousefi M, Pekkala S, Sharifian S, Beyshami G. Shorter recovery time following high-intensity interval training induced higher body fat loss among overweight women. Sport Sciences for Health. 2019;15(1):157-65.
  12. Schonewille M, Freark de Boer J, Mele L, Wolters H, Bloks VW, Wolters JC, et al. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice. Journal of Lipid Research. 2016;57(8):1455-64.
  13. Phulukdaree A, Moodley D, Khan S, Chuturgoon AA. Atorvastatin increases miR-124a expression: a mechanism of Gamt modulation in liver cells. J Cell Biochem. 2015;116(11):2620-7.
  14. Poli A. Atorvastatin: pharmacological characteristics and lipid-lowering effects. Drugs. 2007;67 Suppl 1:3-15.
  15. Clarke AT, Mills PR. Atorvastatin associated liver disease. Dig Liver Dis. 2006;38(10):772-7.
  16. Saavedra K, Leal K, Saavedra N, Prado Y, Paez I, Ubilla CG, et al. MicroRNA-20a-5p Downregulation by Atorvastatin: A Potential Mechanism Involved in Lipid-Lowering Therapy. Int J Mol Sci. 2022;23(9).
  17. Roglans N, Verd JC, Peris C, Alegret M, Vázquez M, Adzet T, et al. High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production. Lipids. 2002;37(5):445-54.
  18. Ikitde NG, Onwuchekwa BU, Akpanyung EO, M. U, Ekanemesang, Oyebadejo SA. Effect of atorvastatin on the liver enzymes, electrolytes and histology of organs in male albino Wistar rats. Biosciences Research in Today’s World. 2015.
  19. Eslami Z, Mirghani SJ, Eghbal Moghanlou A, Norouzi A, Naseh H, Joshaghani H, et al. An Efficient model of Non-alcoholic Fatty Liver Disease (NAFLD) versus current experimental models: effects of fructose, fat, and carbon tetrachloride on NAFLD. Hepat Mon. 2021;21(8):e117696.
  20. Mirghani SJ, Peeri M, Yaghoobpour Yekani O, Zamani M, Feizolahi F, Nikbin S, et al. Role or Synergistic interaction of adenosine and vitamin D3 alongside high-intensity interval training and isocaloric moderate intensity training on metabolic parameters: protocol for an experimental study. JMIR Res Protoc. 2019;8(1):e10753.
  21. Xun T, Rong Y, Lv B, Tian J, Zhang Q, Yang X. Interaction and potential mechanisms between atorvastatin and voriconazole, agents used to treat dyslipidemia and fungal infections. Frontiers in Pharmacology. 2023;14.
  22. Eslami Z, Moghanlou AE, Kandi Y, Arabi MS, Norouzi A, Joshaghani H. Atorvastatin and Flaxseed Effects on Biochemical Indices and Hepatic Fat of NAFLD Model in Rats. Adv Biomed Res. 2023;12:98.
  23. Leandro CG, Levada AC, Hirabara SM, Manhães-de-Castro R, De-Castro CB, Curi R, et al. A program of moderate physical training for Wistar rats based on maximal oxygen consumption. J Strength Cond Res. 2007;21(3):751-6.
  24. Kalaki-Jouybari F, Shanaki M, Delfan M, Gorgani-Firouzjae S, Khakdan S. High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats. Arch Physiol Biochem. 2020;126(3):242-9.
  25. Mirghani SJ, Alinejad HA, Azarbayjani MA, Mazidi A, Mirghani SA. Influence of strength, endurance and concurrent training on the lipid profile and blood testosterone and cortisol response in young male wrestlers. Baltic Journal Of Health And Physical Activity. 2014;6(1).
  26. Pekkala S, Rafiei MM, Eslami Z, Ghaderi M, Moghanlou AE, Sharifian S, et al. High-intensity interval training and moderate intensity training with exogenous adenosine counteract development of obesity in rats. Science & Sports. 2022;37(5):477-85.
  27. Mirghani SJ, Azarbayjani MA, Peeri M, Eslami Z. Effects of endurance training and isocaloric high intensity interval training on anthropometric indices and insulin resistance in high fat diet-fed wistar rats. Medical Laboratory Journal. 2018;12(18).
  28. Wang Y, Guo Y, Xu Y, Wang W, Zhuang S, Wang R, et al. HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice. Metabolites. 2022;13(1).
  29. Yuan Z, Xiao-Wei L, Juan W, Xiu-Juan L, Nian-Yun Z, Lei S. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. J Physiol Biochem. 2022;78(3):641-52.
  30. Mirghani SJ, Yousefi MS. The effect of interval recovery periods during HIIT on liver enzymes and lipid profile in overweight women. Science & Sports. 2015;30(3):147-54.
  31. Motta VF, Aguila MB, Mandarim-de-Lacerda CA. High-intensity interval training beneficial effects in diet-induced obesity in mice: adipose tissue, liver structure, and pancreatic islets. Int J Morphol 2016;34(2):684-91.
  32. Ebrahimi A, Azizi M, Tahmasebi W, Hoseini R. Effect of 8 Weeks of Sodium Alginate Supplementation with HIIT and MICT on Liver Enzymes and Lipid Profile in Men with Metabolic Syndrome. Zahedan J Res Med Sci. 2021;23(4).
  33. Eslami Z, Mohammad nezhad panah kandi Y, Ghaderi M, Eghbal Moghanlou A, Sharifian S, Beyshami G, et al. The effect of endurance training combined with adenosine on the gene expression of UCP-1 and MAPK p38 in subcutaneous adipose tissue of male Wistar rats fed a high -fat diet. Scientific Magazine Yafte. 2023;25(3):66-79.
  34. Eslami Z, Mohammadnajad PanahKandi Y, Sharifian S, Eghbal Moghanlou A, Sheikh SR, Mirghani SJ. Evaluation of the effect of aerobic exercise on UCP1 and MAPK p38 heat factor gene expression in subcutaneous adipose tissue in male Wistar rats fed a high-fat diet. Feyz Medical Sciences Journal. 2021;25(4):1020-30.
  35. Mirghani SJ, Azarbayjani MA, Peeri M, Eslami Z, keshtkar A. Interaction Effect of Vitamin D Injection during a Course of Endurance Training on Anthropometrical Parameters with High-Fat Diet-Induced Obesity in Wistar Rats. Medical Laboratory Journal 2019;13(6).
  36. Ji G, Zhao X, Leng L, Liu P, Jiang Z. Comparison of dietary control and atorvastatin on high fat diet induced hepatic steatosis and hyperlipidemia in rats. Lipids Health Dis. 2011;10:23.
Journal of Nutrition,Fasting and Health
Volume 12, Issue 3
Summer 2024
Pages 159-165

  • Receive Date 02 October 2023
  • Revise Date 05 January 2024
  • Accept Date 06 January 2024