Journal of Kerman University of Medical Sciences

Effect of Exercise Training and L-Carnitine on Mitochondrial Dynamics and Antioxidant Status in the Liver of Male Wistar Rats

Document Type : Original Article

Authors

Soheil Aminizadeh 1
Beydolah Shahouzehi 2

1 Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

2 1. Student Research Committee, Kerman University of Medical Sciences, Kerman,

https://doi.org/10.34172/jkmu.4247
Abstract

Introduction: The liver is a very important organ, which is involved in processes such as gluconeogenesis, protein synthesis, glycogen storage, and detoxification. Mitochondrial dynamics, governed by proteins involved in fusion and fission, play a crucial role in maintaining liver functionality. Impaired mitochondrial dynamics and elevated oxidative stress contribute to hepatic pathology and metabolic imbalance.
Methods: This study investigated the independent and combined effects of intraperitoneal L-carnitine supplementation and performing high-intensity interval training (HIIT) on hepatic gene expression related to mitochondrial dynamics and antioxidant defense in male Wistar rats. A total of 32 rats were assigned to four groups: Control, L-carnitine, HIIT, and HIIT-L-carnitine combination. Following the intervention period, liver tissues were collected to assess the expression levels of key genes involved in mitochondrial dynamics and oxidative stress regulation.
Results: It was found that both HIIT and L-carnitine supplementation independently enhanced mitochondrial fusion in the liver, with significant increases in OPA1 expression (P < 0.001 for HIIT vs. control and P = 0.007 for L-carnitine vs. control). The combined intervention further amplified this effect, with OPA1 expression significantly upregulated compared with the L-carnitine group (P = 0.044). The combination of HIIT – L-carnitine significantly reduced both FIS1 and DRP1 compared with controls (P < 0.001). Additionally, antioxidant-related genes NRF2 (P < 0.01) and HO-1 were upregulated by each intervention, with the combined group showing additive effects (P < 0.001).
Conclusion: These findings highlight the potential of integrating exercise and nutritional supplementation as non-pharmacological strategies to optimize mitochondrial dynamics and enhance oxidative resilience, even in non-pathological conditions.

Highlights

Beydolah Shahouzehi (Google Scholar)(PubMed)

 Soheil Aminizadeh (Google Scholar)(PubMed)

 

Keywords

Mitochondria
Carnitine
High-intensity interval training
Mitofusins
Dynamin-related protein 1
Subjects
 
1.                    Lee H, Lee TJ, Galloway CA, Zhi W, Xiao W, de Mesy Bentley KL, et al. The mitochondrial fusion protein OPA1 is dispensable in the liver and its absence induces mitohormesis to protect liver from drug-induced injury. Nat Commun 2023;14(1):6721. doi:10.1038/s41467-023-42564-0
2.                    Zhou Y, Long D, Zhao Y, Li S, Liang Y, Wan L, et al. Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation. Cell Death Dis 2022;13(8):689. doi:10.1038/s41419-022-05088-x
3.                    Wang L, Ishihara T, Ibayashi Y, Tatsushima K, Setoyama D, Hanada Y, et al. Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration. Diabetologia 2015;58(10):2371-80. doi:10.1007/ s00125-015-3704-7
4.                    Lim AY, Chen YC, Hsu CC, Fu TC, Wang JS. The effects of exercise training on mitochondrial function in cardiovascular diseases: a systematic review and meta-analysis. Int J Mol Sci 2022;23(20):12559. doi:10.3390/ijms232012559
5.                    Li R, Toan S, Zhou H. Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease. Aging (Albany NY) 2020;12(7):6467-85. doi:10.18632/aging.102972
6.                    Ruegsegger GN, Pataky MW, Simha S, Robinson MM, Klaus KA, Nair KS. High-intensity aerobic, but not resistance or combined, exercise training improves both cardiometabolic health and skeletal muscle mitochondrial dynamics. J Appl Physiol (1985) 2023;135(4):763-74. doi:10.1152/japplphysiol.00405.2023
7.                    Xu D, Xu M, Jeong S, Qian Y, Wu H, Xia Q, et al. The role of Nrf2 in liver disease: novel molecular mechanisms and therapeutic approaches. Front Pharmacol 2018;9:1428. doi:10.3389/fphar.2018.01428
8.                    Montesano A, Senesi P, Vacante F, Mollica G, Benedini S, Mariotti M, et al. L-carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers. J Endocrinol Invest 2020;43(4):493-503. doi:10.1007/ s40618-019-01134-2
9.                  Portela FS, Malheiro LFL, Oliveira CA, Mercês ÉA, De Benedictis LM, De Benedictis JM, et al. High-intensity interval training improves hepatic redox status via Nrf2 downstream pathways and reduced CYP2E1 expression in female rats with cisplatin-induced hepatotoxicity. Food Chem Toxicol 2025;196:115234. doi:10.1016/j.fct.2024.115234
10. Souza-Tavares H, Santana-Oliveira DA, Vasques-Monteiro IML, Silva-Veiga FM, Mandarim-de-Lacerda CA, Souza-Mello V. Exercise enhances hepatic mitochondrial structure and function while preventing endoplasmic reticulum stress and metabolic dysfunction-associated steatotic liver disease in mice fed a high-fat diet. Nutr Res 2024;126:180-92. doi:10.1016/j. nutres.2024.04.002
11. Coyle EF. Very intense exercise-training is extremely potent and time efficient: a reminder. J Appl Physiol (1985) 2005;98(6):1983-4. doi:10.1152/japplphysiol.00215.2005
12. 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):14. doi:10.3390/metabo13010014
13. Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol Respir Environ Exerc Physiol 1984;56(4):831-8. doi:10.1152/jappl.1984.56.4.831
14. Gibala MJ, Little JP, van Essen M, Wilkin GP, Burgomaster KA, Safdar A, et al. Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. J Physiol 2006;575(Pt 3):901- 11. doi:10.1113/jphysiol.2006.112094
15. Gaesser GA, Angadi SS. High-intensity interval training for health and fitness: can less be more? J Appl Physiol (1985) 2011;111(6):1540-1. doi:10.1152/japplphysiol.01237.2011
16. Cha YS. Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pac J Clin Nutr 2008;17 Suppl 1:306-8.
17. Shahouzehi B, Nasri H, Aminizadeh S, Masoumi-Ardakani Y. The effect of high-intensity interval training and L-carnitine on the expression of some pro-inflammatory genes in the liver and cardiac tissues of rats. J Kerman Univ Med Sci 2021;28(1):56- 68. doi:10.22062/jkmu.2021.91564
18. Choi JW, Ohn JH, Jung HS, Park YJ, Jang HC, Chung SS, et al. Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction. Metabolism 2018;78:43- 51. doi:10.1016/j.metabol.2017.09.005
19. Sawicka AK, Renzi G, Olek RA. The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr 2020;17(1):49. doi:10.1186/s12970-020-00377-2
20. Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci 2022;23(5):2717. doi:10.3390/ijms23052717
21. Masoumi-Ardakani Y, Aminizadeh S, Fallah H, Shahouzehi B. L-carnitine different doses affect serum and pancreas tissue antioxidative defense and histopathology in STZ-induced diabetic rats. Biologia 2020;75(9):1415-23. doi:10.2478/ s11756-020-00432-y
22. Lee JK, Lee JS, Park H, Cha YS, Yoon CS, Kim CK. Effect of L-carnitine supplementation and aerobic training on FABPc content and beta-HAD activity in human skeletal muscle. Eur J Appl Physiol 2007;99(2):193-9. doi:10.1007/s00421-006- 0333-3
23. Sobhani V, Mirdar S, Arabzadeh E, Hamidian G, Mohammadi F. High-intensity interval training-induced inflammation and airway narrowing of the lung parenchyma in male maturing rats. Comp Clin Path 2018;27(3):577-82. doi:10.1007/s00580- 017-2630-0
24. Shahouzehi B, Masoumi-Ardakani Y, Fallah H, Aminizadeh S. Concomitant administration of L-carnitine and performing high-intensity interval training effects on the genes involved in mitochondrial fusion and apoptosis in rat liver. Jordan J Biol Sci 2023;16(1):21-6. doi:10.54319/jjbs/160104
25. Fallah H, Masoumi-Ardakani Y, Pourkamalzadeh M, Shahouzehi B. Antioxidant effects of pioglitazone and interleukin-1 receptor-associated kinase inhibition on oxidative stress indices in obese C57BL/6J mice. J Kerman Univ Med Sci 2025;32(1):1-7. doi:10.34172/jkmu.4145
 
 
Journal of Kerman University of Medical Sciences
Volume 33
Pages 1-7

Home

Editorial Board

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us