The impact of aerobic exercise and Iranian ethanolic extract of bitter orange peel on PGC-1α gene expression in the liver tissue of obese female Wistar rats
Subject Areas : Physical Activity and HealthAmir Hesam Salmasi Fard 1 , Mohammad Ali Azarbayjani 2 * , فرهاد ریاضی راد 3 , maghsoud peeri 4 , حسن متین همایی 5
1 - Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
2 - Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
3 - TarbiatModares University, Tehran, Iran
4 - department of physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
5 - Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
Keywords: aerobic training, orange peel, PGC-1α, obesity,
Abstract :
Objective: The present study investigated the simultaneous effect of aerobic training and bitter orange peel on PGC-1α in the liver tissue of obese female Wistar rats. Methods: For this study, Wistar rats were randomly divided into 5 groups of 6: healthy control, obese, obese+AT, obese+extract, and obese+AT+extract, and obesity protocol was applied. Aerobic training (AT) was done 5 days a week for 30 minutes with moderate intensity. Ethanol extract of bitter orange peel with a dose of 60 mg per kg of the rat's weight was administered by gavage for 6 weeks. The rats were sacrificed 48 hours after completing the protocols, and the liver tissue was removed and immediately frozen at -80. The real-time PCR method expressed the PGC-1α gene in liver tissue. For data analysis, independent t-tests and two-way analyses of variance ANOVA were performed using GraphPad Prism version 10 software with a significance level of p=0.05. Findings: The results showed that obesity caused a significant decrease in PGC-1α gene expression compared to the healthy control group (p=0.001). There was a significant difference in the expression of PGC-1α between the AT group, AT+bitter orange peel, and ethanol extract of orange peel with the obese group and healthy control (p=0.001); the highest expression was related to the group of AT+bitter orange peel ethanol extract. Conclusion: According to the research findings, aerobic training and the consumption of bitter orange can help reduce hepatocyte damage caused by a high-fat diet and obesity by enhancing the expression of the PGC-1α gene.
Akashi, S., Morita, A., Mochizuki, Y., Shibuya, F., Kamei, Y., & Miura, S. (2021). Citrus hassaku Extract Powder Increases Mitochondrial Content and Oxidative Muscle Fibers by Upregulation of PGC-1α in Skeletal Muscle. Nutrients, 13(2). https://doi.org/10.3390/nu13020497
Assini, J. M., Mulvihill, E. E., Burke, A. C., Sutherland, B. G., Telford, D. E., Chhoker, S. S., Sawyez, C. G., Drangova, M., Adams, A. C., Kharitonenkov, A., Pin, C. L., & Huff, M. W. (2015). Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21. Endocrinology, 156(6), 2087-2102. https://doi.org/10.1210/en.2014-2003
Assini, J. M., Mulvihill, E. E., & Huff, M. W. (2013). Citrus flavonoids and lipid metabolism. Current opinion in lipidology, 24(1), 34-40.
https://doi.org/10.1097/MOL.0b013e32835c07fd Assini, J. M., Mulvihill, E. E., Sutherland, B. G., Telford, D. E., Sawyez, C. G., Felder, S. L., Chhoker, S., Edwards, J. Y., Gros, R., & Huff, M. W. (2013). Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S]. Journal of Lipid
Research, 54(3), 711-724. https://doi.org/https://doi.org/10.1194/jlr.M032631 Bianchi, A., Marchetti, L., Hall, Z., Lemos, H., Vacca, M., Paish, H., Green, K., Elliott, B., Tiniakos, D., Passos, J. F., Jurk, D., Mann, D. A., & Wilson, C. L. (2021). Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis. The Journal of Immunology, 206(4), 904-
916. https://doi.org/10.4049/jimmunol.2001022 Cheng, C.-F., Ku, H.-C., & Lin, H. (2018). PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation. International journal of molecular sciences, 19(11).
https://doi.org/10.3390/ijms19113447 Dethlefsen, M., Kristensen, C., Tøndering, A., Lassen, S., Ringholm, S., & Pilegaard, H. (2018). Impact of liver PGC-1α on exercise and exercise training-
induced regulation of hepatic autophagy and mitophagy in mice on HFF. Physiological Reports, 6, e13731-e13731. https://doi.org/10.14814/phy2.13731 Eftekharzadeh, M., Atashak, S., Azarbayjani, M. A., Moradi, L., & Rahmati-Ahmadabad, S. (2023). The Effect of Aerobic Exercise on SREBP-1c Gene
Expression in Skeletal Muscle in Obese Female Rats [Research Article]. Thrita, 12(1), e138382. https://doi.org/10.5812/thrita-138382 Font-Burgada, J., Sun, B., & Karin, M. (2016). Obesity and Cancer: The Oil that Feeds the Flame. Cell Metabolism, 23(1), 48-62.
https://doi.org/10.1016/j.cmet.2015.12.015 Guo, J., Tao, H., Cao, Y., Ho, C.-T., Jin, S., & Huang, Q. (2016). Prevention of Obesity and Type 2 Diabetes with Aged Citrus Peel (Chenpi) Extract. Journal of
Agricultural and Food Chemistry, 64(10), 2053-2061. https://doi.org/10.1021/acs.jafc.5b06157 Hawley, J. A., Hargreaves, M., Joyner, M. J., & Zierath, J. R. (2014). Integrative biology of exercise. Cell, 159(4), 738-749.
https://doi.org/10.1016/j.cell.2014.10.029 Hu, M., Zhang, L., Ruan, Z., Han, P., & Yu, Y. (2021). The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-
Alcoholic Fatty Liver Disease (NAFLD). Foods (Basel, Switzerland), 10(12). https://doi.org/10.3390/foods10123022 Kang, S., Song, S., Lee, J., Chang, H., & Lee, S. (2018). Clinical Investigations of the Effect of Citrus unshiu Peel Pellet on Obesity and Lipid Profile.
Evidence-Based Complementary and Alternative Medicine, 2018, 4341961-4341961. https://doi.org/10.1155/2018/4341961 Khayampour, N., Peeri, M., & Azarbayjani, M. A. (2023). A Comparative Analysis of Two High-Intensity Interval Training (HIIT) Programs on PGC-1α, p53, and Citrate Synthase Protein Levels in Cardiomyocytes of Male Type 2 Diabetic Rats [Research]. Journal of Basic Research in Medical Sciences, 10(4), 54-
66. http://jbrms.medilam.ac.ir/article-1-671-en.html Kianmehr, P., Azarbayjani, M. A., Peeri, M., & Farzanegi, P. (2020). Synergic effects of exercise training and octopamine on peroxisome proliferator-activated receptor-gamma coactivator -1a and uncoupling protein 1 mRNA in heart tissue of rat treated with deep frying oil. Biochemistry and
Biophysics Reports, 22, 100735-100735. https://doi.org/10.1016/J.BBREP.2020.100735 Koolaji, N., Shammugasamy, B., Schindeler, A., Dong, Q., Dehghani, F., & Valtchev, P. (2020). Citrus Peel Flavonoids as Potential Cancer Prevention
Agents. Current Developments in Nutrition, 4(5). https://doi.org/10.1093/CDN/NZAA025 Lee, G.-H., Peng, C., Park, S.-A., Hoang, T.-H., Lee, H.-Y., Kim, J., Kang, S.-I., Lee, C.-H., Lee, J.-S., & Chae, H.-J. (2020). Citrus Peel Extract Ameliorates High-
Fat Diet-Induced NAFLD via Activation of AMPK Signaling. Nutrients, 12(3). https://doi.org/10.3390/nu12030673 Melo, L., Tilmant, K., Hagar, A., & Klaunig, J. E. (2021). Effect of endurance exercise training on liver gene expression in male and female mice.
367(March), 356-367. Mohammed, M. S., Sendra, S., Lloret, J., & Bosch, I. (2018). Systems and WBANs for Controlling Obesity. Journal of healthcare engineering, 2018, 1564748-
1564748. https://doi.org/10.1155/2018/1564748 Qian, L., Zhu, Y., Deng, C., Liang, Z., Chen, J., Chen, Y., Wang, X., Liu, Y., Tian, Y., & Yang, Y. (2024). Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases. Signal Transduction and Targeted Therapy, 9(1), 50-50.
https://doi.org/10.1038/s41392-024-01756-w Shamsnia, E., Matinhomaee, H., Azarbayjani, M. A., & Peeri, M. (2023). The Effect of Aerobic Exercise and Bitter Orange Peel Extract on Oxidative Biomarkers and the Nrf2-Keap1 Signaling Pathway in the Quadriceps Tissue of Male Rats Fed a High-Fat Diet [Research Article]. Gene Cell Tissue, 11(1),
e138980. https://doi.org/10.5812/gct-138980 Shen, S.-H., Singh, S. P., Raffaele, M., Waldman, M., Hochhauser, E., Ospino, J., Arad, M., & Peterson, S. J. (2022). Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion. Antioxidants (Basel, Switzerland),
11(6). https://doi.org/10.3390/antiox11061147 Song, J., Kim, D.-Y., Lee, H. S., Rhee, S. Y., & Lim, H. (2024). Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A
12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 16(4). https://doi.org/10.3390/nu16040494 Stevanović, J., Beleza, J., Coxito, P., Ascensão, A., & Magalhães, J. (2020). Physical exercise and liver “fitness”: Role of mitochondrial function and epigenetics-related mechanisms in non-alcoholic fatty liver disease. Molecular Metabolism, 32, 1-14.
https://doi.org/https://doi.org/10.1016/j.molmet.2019.11.015 Sun, M., Zhao, X., Li, X., Wang, C., Lin, L., Wang, K., Sun, Y., Ye, W., Li, H., Zhang, Y., & Huang, C. (2023). Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways. Journal of
inflammation research, 16, 4805-4819. https://doi.org/10.2147/JIR.S426581 Takahashi, H., Kotani, K., Tanaka, K., Egucih, Y., & Anzai, K. (2018). Therapeutic Approaches to Nonalcoholic Fatty Liver Disease: Exercise Intervention
and Related Mechanisms. Frontiers in Endocrinology, 9, 588-588. https://doi.org/10.3389/fendo.2018.00588 Wen, X., Zhang, B., Wu, B., Xiao, H., Li, Z., Li, R., Xu, X., & Li, T. (2022). Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal
Transduction and Targeted Therapy, 7(1), 298-298. https://doi.org/10.1038/s41392-022-01149-x Wu, H., Kanatous, S. B., Thurmond, F. A., Gallardo, T., Isotani, E., Bassel-Duby, R., & Williams, R. S. (2002). Regulation of mitochondrial biogenesis in
skeletal muscle by CaMK. Science (New York, N.Y.), 296(5566), 349-352. https://doi.org/10.1126/science.1071163