Effect of Moderate Aerobic Exercise Combined with Cannabinoid Supplementation on P53 Gene Expression in Rats with High-Fat Diet-Induced Non-alcoholic fatty liver disease (NAFLD)
الموضوعات :
Masoumeh Mohamadkhani
1
,
Mandana Gholami
2
,
Heshmatolah Parsian
3
1 - Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Department of Physical Education and Sport Sciences, shahr-e-Qods Branch, Islamic Azad University, Iran.
الکلمات المفتاحية: Cannabinoid supplements, exercise, high-fat diet, Non-alcoholic fatty liver disease (NAFLD),
ملخص المقالة :
Introduction: In the present study, changes in P53 gene expression were investigated in rats fed a high-fat diet (HFD) after 6 weeks of moderate aerobic exercise and cannabinoid supplementation.
Method: In this experimental study, 40 male Wistar rats were divided into 5 groups (n=8 per group): healthy control, high-fat diet (HFD), HFD + aerobic exercise (Tr), HFD + cannabinoid supplement (Sup), and HFD + Tr + Sup. Rats in the HFD group received a special high-fat diet for 2 months before the main protocol. Rats in the exercise groups ran on a rodent treadmill for 6 weeks, 5 days per week. Cannabinoids supplements were administered via gavage at a dose of 100 ng/kg after each exercise session to rats in the supplement group. To confirm Non-alcoholic fatty liver disease (NAFLD) induction based on HFD, the rats’ livers were examined using a Zonecare-Q9 ultrasound device before the start of the exercise and supplementation protocol. Finally, after the exercise and supplementation protocol, the rats were sacrificed, and the P53 variable was measured by Real-Time PCR. For data analysis, an independent t-test, Bonferroni test, and two-way ANOVA were used.
Results: Ultrasound results showed that the high-fat diet in the HFD group induced grade 2 Non-alcoholic fatty liver disease (NAFLD) compare to the healthy control group. In the HFD group, the P53 gene expression in liver tissue was significantly increased in comparison to the healthy control group (p<0.05). Compared to the HFD group, the Sup group showed a significant decrease in P53 (p<0.05). The HFD+Tr and HFD+Tr+Sup groups did not demonstrate a significant effect on P53 in comparison to the HFD group (p<0.05).
Conclusion: The high-fat diet can lead to grade 2 Non-alcoholic fatty liver disease (NAFLD), while cannabinoid supplements, by reducing cellular stress and modulating P53 gene expression, may improve cellular signaling processes and provide a basis for developing new therapeutic strategies for liver cancer patients
Arfianti A, Pok S, Barn V, Haigh WG, Yeh MM, Ioannou GN, et al. Exercise retards hepatocarcinogenesis in obese mice independently of weight control. J Hepatol (2020) 73(1):140–48. doi: 10.1016/j.jhep.2020.02.006
Azar, S., Udi, S., Drori, A., Hadar, R., Nemirovski, A., Vemuri, K. V., Miller, M., Sherill-Rofe, D., Arad, Y., Gur-Wahnon, D., Li, X., Makriyannis, A., Ben-Zvi, D., Tabach, Y., Ben-Dov, I. Z., & Tam, J. (2020). Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent. Molecular Metabolism, 42, 101087. https://doi.org/10.1016/j.molmet.2020.101087
Cai-Yu, Lian, et al. (2020). High fat diet-triggered non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease: A review of proposed mechanisms. Chemico-Biological Interactions, 330, 109199. https://doi.org/10.1016/j.cbi.2020.109199
Cook, J. J., Wei, M., Segovia, B., Cosio-Lima, L., Simpson, J., Taylor, S., Koh, Y., Kim, S., & Lee, Y. (2022). Endurance exercise-mediated metabolic reshuffle attenuates high-caloric diet-induced non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease. Annals of Hepatology, 22, 100709. https://doi.org/10.1016/j.aohep.2022.100709
Cui, N., Li, H., Dun, Y., Ripley-Gonzalez, J. W., Wang, J., & Zhang, Y. (2022). Exercise inhibits JNK pathway activation and lipotoxicity via macrophage migration inhibitory factor in nonalcoholic Non-alcoholic fatty liver disease (NAFLD) disease. Frontiers in Endocrinology, 13, 961231. https://doi.org/10.3389/fendo.2022.961231
Institute for Health Metrics and Evaluation (IHME). (2017). Global burden of disease study 2015 (GBD 2015) obesity and overweight prevalence 1980–2015. Seattle, United States: Institute for Health Metrics and Evaluation.
Jeon, Y., Kim, T., Kwon, H., Kim, J. K., Park, Y. T., Ham, J., & Kim, Y. J. (2023). Cannabidiol enhances cabozantinib-induced apoptotic cell death via phosphorylation of p53 regulated by ER stress in hepatocellular carcinoma. Cancers, 15, 3987. https://doi.org/10.3390/cancers15063987
Jiang, M., et al. (2013). Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease. Proceedings of the National Academy of Sciences, 110(10), 4274–4279. https://doi.org/10.1073/pnas.1307233110
Krstic, J., Galhuber, M., Schulz, T. J., Schupp, M., & Prokesch, A. (2018)b. P53 as a dichotomous regulator of liver disease: The dose makes the medicine. International Journal of Molecular Sciences, 19(3), 921. https://doi.org/10.3390/ijms19030921
Krstic, J., Reinisch, I., Schupp, M., Schulz, T. J., & Prokesch, A. (2018) a. P53 functions in adipose tissue metabolism and homeostasis. International Journal of Molecular Sciences, 19(9), 2622. https://doi.org/10.3390/ijms19092622
Li, Y., Wu, L., & Huang, H. (2020) b. p53 as a double-edged sword in the progression of non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease. Frontiers in Pharmacology, 11, 607. https://doi.org/10.3389/fphar.2020.00607
Lian, C.-Y., Zhai, Z.-Z., Li, Z.-F., & Wang, L. (2020). High fat diet-triggered non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease: A review of proposed mechanisms. Chemico-Biological Interactions, 330, 109199. https://doi.org/10.1016/j.cbi.2020.109199
Liu, Y., et al. (2020). Exercise retards hepatocarcinogenesis in obese mice. Journal of Hepatology, 73(1), 83–92. https://doi.org/10.1016/j.jhep.2020.01.023
Pacher, P., Bátkai, S., & Kunos, G. (2008). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews, 58(3), 389–462. https://doi.org/10.1124/pr.58.3.2
Sproesser, G., Ruby, M. B., Arbit, N., Akotia, C. S., Alvarenga, M. d. S., Bhangaokar, R., … Kaptan, G. (2019). Understanding traditional and modern eating: the TEP10 framework. BMC Public Health, 19, 1–14. https://doi.org/10.1186/s12889-019-7390-3
Strycharz, J., Drzewoski, J., Szemraj, J., & Sliwinska, A. (2017). Is P53 involved in tissue-specific insulin resistance formation? Oxidative Medicine and Cellular Longevity, 2017, 9270549. https://doi.org/10.1155/2017/9270549
Štern, A., Novak, M., Kološa, K., Trontelj, J., Žabkar, S., Šentjurc, T., Filipič, M., & Žegura, B. (2024). Exploring the safety of cannabidiol (CBD): A comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa L. Biomedicine & Pharmacotherapy, 116, 116969. https://doi.org/10.1016/j.biopha.2024.116969
Wang, X., Zhao, X., Gao, X., Mei, Y., & Wu, M. (2013). A new role of p53 in regulating lipid metabolism. Journal of Molecular Cell Biology, 5(2), 147–150. https://doi.org/10.1093/jmcb/mjs064
Yan, Z., Miao, X., Zhang, B., & Xie, J. (2018). P53 as a double-edged sword in the progression of NAFLD. Life Sciences, 215, 64–72. https://doi.org/10.1016/j.lfs.2018.10.051
Zwezdaryk, K., Sullivan, D., & Saifudeen, Z. (2018). The P53/Adipose-Tissue/Cancer nexus. Frontiers in Endocrinology, 9, 457. https://doi.org/10.3389/fendo.2018.00457
Zhang, Y., et al. (2022). Effects of exercise on high-fat diet–induced non-alcoholic Non-alcoholic fatty liver disease (NAFLD) disease in mice. Nutrition & Metabolism. https://doi.org/10.1186/s12986-022-00644-w
