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 : گیاهان دارویی و ورزش
Masoumeh Mohamadkhani
1
,
Mandana Gholami
2
,
Heshmatolah Parsian
3
,
Hossein Abednatanzi
4
1 - Department of Physical Education and Sport Sciences, SR.C., Islamic Azad University, Tehran, Iran
2 - Department of Physical Education and Sport Sciences, SR.C., Islamic Azad University, Tehran, Iran
3 - Department of Physical Education and Sport Sciences, shahr-e-Qods Branch, Islamic Azad University, Iran.
4 - Department of Physical Education and Sport Sciences, SR.C., Islamic Azad University, Tehran, 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.
Methods: 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.
1. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627–2642. doi:10.1016/S0140-6736(17)32129-3.
2. GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27. doi:10.1056/NEJMoa1614362.
3. Hruby A, Hu FB. The epidemiology of obesity: a big picture. PharmacoEconomics. 2015;33(7):673–689. doi:10.1007/s40273-014-0243-x.
4. Cai Y, Lian J. Mechanisms of non-alcoholic fatty liver disease progression. World J Gastroenterol. 2020;26(45):689–703. doi:10.3748/wjg.v26.i45.689.
5. Zwezdaryk KJ, Sullivan DE, Saifudeen Z. The p53 pathway in metabolic disease. J Endocrinol. 2018;238(2):R1–R12. doi:10.1530/JOE-18-0148.
6. Strycharz J, Drzewoski J, Szemraj J, Sliwinska A. Is p53 involved in tissue-specific insulin resistance formation? Cell Physiol Biochem. 2017;41(3):873–883. doi:10.1159/000458734.
7. Krstić J, Reinisch I, Schupp M, Schulz TJ, Prokesch A. p53 functions in adipose tissue metabolism and homeostasis. Cell Mol Life Sci. 2018;75(9):175–193. doi:10.1007/s00018-017-2676-8.
8. Krstić J, Galhuber M, Schulz TJ, Schupp M, Prokesch A. p53 as a dichotomous regulator of metabolism. Biochim Biophys Acta Mol Basis Dis. 2018;1864(9 Pt B):3166–3178. doi:10.1016/j.bbadis.2018.01.034.
9. Li Y, Wu D, Huang Q. Inhibition of p53 alleviates hepatic steatosis and inflammation in high-fat diet–induced NAFLD mice. Biochem Biophys Res Commun. 2020;521(1):213–219. doi:10.1016/j.bbrc.2019.10.079.
10. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2008;60(3):389–462. doi:10.1124/pr.108.000869.
11. Azar S, et al. Endocannabinoid signaling via CB1 receptor regulates hepatic p53/miR-22/SIRT1 axis in steatosis. Hepatology. 2020;72(4):1234–1248. doi:10.1002/hep.31145.
12. Zhang HJ, Pan LL, Ma ZM, Chen Z, Huang ZF, Sun Q, et al. Long-term exercise improves liver lipid metabolism in NAFLD. J Hepatol. 2020;73(1):146–156. doi:10.1016/j.jhep.2020.02.022.
13. Liu Y, et al. Exercise-induced modulation of p53 signaling protects against liver injury. Redox Biol. 2020;34:101563. doi:10.1016/j.redox.2020.101563.
14. Sproesser G, Ruby MB, Arbit N, Akotia CS, Alvarenga MS, Bhangaokar R, et al. Understanding traditional and modern eating patterns. Nutrients. 2019;11(7):150. doi:10.3390/nu11071500.
15. Lian J, et al. Dietary patterns and non-alcoholic fatty liver disease. Nutrients. 2020;12(9):278. doi:10.3390/nu12090278.
16. Yan H, et al. Role of p53 in hepatic lipid metabolism and NAFLD. Biomed Pharmacother. 2018;103:153–161. doi:10.1016/j.biopha.2018.04.036.
17. Jiang Z, et al. Activation of p53 mediates hepatic injury in high-fat diet–induced fatty liver disease. Hepatology. 2013;58(1):219–229. doi:10.1002/hep.26339.
18. Naghizadeh N, Riyahi Malayeri S, Roozbahani M, Khademi A, Shirvani H. The effectiveness of endurance training and nano-curcumin supplementation on the expression of miR-21 and p53 genes in brain tumor tissue in an animal model of glioblastoma multiforme. J Nutr Fasting Health. 2024;12(1):26–35. doi:10.22038/jnfh.2023.73964.1455.
19. Riyahi Malayeri S, Hoseini M. The effect of acute exercise on vaspin and chemerin levels in obese men. J Basic Res Med Sci. 2021;8(1):58–66.
20. Ghane M, Riyahi Malayeri S, Hosseini M. High-intensity interval training and nano-selenium supplementation on hepatic SOD and CAT gene expression in dexamethasone-induced rats. Sport Sci Health. 2024;20(2):177–184. doi:10.1007/s11332-023-01087-3.
21. Ghoochani S, Riyahi Malayeri S, Daneshjo A. Short-term effect of citrulline malate supplementation on LDH and lactate levels and resistance exercise performance. J Mil Med. 2022;22(4):154–162.
22. Maleki S, Azarbayjani MA, Riyahi Malayeri S, Peeri M, Rahmati Ahmadabad S. The effect of aerobic exercise and ethanolic extract of rice bran on the expression of acetyl-CoA carboxylase and HMGCR genes in the liver tissue of rats fed a high-fat diet. KMAN Health Nutr. 2024;2(3). doi:10.61838/kman.hn.2.3.11.