Mon, Apr 21, 2025
Mahshad Paziraee1 
, Habib Asgharpour2 , Asra Askari3 , Reza Rezaei Shirazi1 , Neda Aghaei Bahman Beglo4
, Habib Asgharpour2 , Asra Askari3 , Reza Rezaei Shirazi1 , Neda Aghaei Bahman Beglo4
1- Department of Physical Education & sports sciences, Aliabad katoul Branch, Islamic Azad University, Aliabad katoul, Iran
2- Department of Physical Education & sports sciences, Aliabad katoul Branch, Islamic Azad University, Aliabad katoul, Iran ,Habib.asgharpour@gmail.com
3- Department of Physical Education & sports sciences, Gorgan Branch, Islamic Azad University, Gorgan, Iran
4- Islamic Azad University
2- Department of Physical Education & sports sciences, Aliabad katoul Branch, Islamic Azad University, Aliabad katoul, Iran ,
3- Department of Physical Education & sports sciences, Gorgan Branch, Islamic Azad University, Gorgan, Iran
4- Islamic Azad University
Abstract: (576 Views)
Background and objectives: The purpose of this research is to investigate continuous exercise and starvation in regulating the activity of the apoptotic pathway caused by endoplasmic reticulum stress in the liver of male Wistar non-alcoholic fatty model rats.
Methods :30 Wistar male obese rats, 18-20 weeks old, with an average body weight of 348 ± 25.53, , were selected as research samples. After one week familiarization with the laboratory environment, the fatty model animals were randomly divided into 6 groups of 5 Rat. The entire training course includes two familiarization stages (one week of adaptation to the research environment and treadmill) and the main training (for 4 weeks, 3 and 5 days a week for 45-60 minutes) on a treadmill with zero grade. The statistical test of one-way analysis of variance was used at a significance level of less than 0.05 and the LSD post hoc test was used among the research groups.
Results: According to the statistical results of the one-way analysis of variance, it showed a significant decrease in the ratio of lipoproteins (VLDL/HDL, LDL/HDL) in all experimental groups compared to the control group, and also a significant decrease in XBP1 and CHOP gene expression in the 5-day training groups. He showed 3-5 days of training with hunger.
Conclusion: Therefore, regular exercise along with starvation can prevent the progression of NAFLD by suppressing the excessive stress activity of the endoplasmic reticulum.
Methods :30 Wistar male obese rats, 18-20 weeks old, with an average body weight of 348 ± 25.53, , were selected as research samples. After one week familiarization with the laboratory environment, the fatty model animals were randomly divided into 6 groups of 5 Rat. The entire training course includes two familiarization stages (one week of adaptation to the research environment and treadmill) and the main training (for 4 weeks, 3 and 5 days a week for 45-60 minutes) on a treadmill with zero grade. The statistical test of one-way analysis of variance was used at a significance level of less than 0.05 and the LSD post hoc test was used among the research groups.
Results: According to the statistical results of the one-way analysis of variance, it showed a significant decrease in the ratio of lipoproteins (VLDL/HDL, LDL/HDL) in all experimental groups compared to the control group, and also a significant decrease in XBP1 and CHOP gene expression in the 5-day training groups. He showed 3-5 days of training with hunger.
Conclusion: Therefore, regular exercise along with starvation can prevent the progression of NAFLD by suppressing the excessive stress activity of the endoplasmic reticulum.
Research Article: Research Article |
Subject:
Sport Physiology
Received: 2023/11/22 | Accepted: 2023/12/13
Received: 2023/11/22 | Accepted: 2023/12/13
References
1. Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025; PMID: 30571059. [View at Publisher] [PMID] [Google Scholar]
2. Heeren J, Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism. Mol Metab. 2021; 50:101238. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Todosenko N, Khaziakhmatova O, Malashchenko V, Yurova K, Bograya M, Beletskaya M, Vulf M, Gazatova N, Litvinova L. Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity. Int J Mol Sci. 2023; 24(15): 12012. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Ge X, Zheng L, Wang M, Du Y, Jiang J. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990-2017: a population-based observational study. BMJ Open. 2020; 10(8): e036663. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Chen YY, Yeh MM. Non-alcoholic fatty liver disease: A review with clinical and pathological correlation. J Formos Med Assoc. 2021; 120(1 Pt 1): 68-77. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Caussy C, Aubin A, Loomba R. The Relationship Between Type 2 Diabetes, NAFLD, and Cardiovascular Risk. Curr Diab Rep. 2021; 21(5): 15. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Fang YL, Chen H, Wang CL, Liang L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From "two hit theory" to "multiple hit model". World J Gastroenterol. 2018; 24(27): 2974-2983. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Zhou L, Shen H, Li X, Wang H. Endoplasmic reticulum stress in innate immune cells - a significant contribution to non-alcoholic fatty liver disease. Front Immunol. 2022;13:951406. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Sandes JM, de Figueiredo RCBQ. The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy. Front Cell Infect Microbiol. 2022; 12:1057774. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Hu H, Tian M, Ding C, Yu S. The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection. Front Immunol. 2019; 9: 3083. [View at Publisher] [DOI] [PMID] [Google Scholar]
11. Choi JA, Song CH. Insights Into the Role of Endoplasmic Reticulum Stress in Infectious Diseases. Front Immunol. 2020; 10: 3147. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Bhattarai KR, Riaz TA, Kim HR, Chae HJ. The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling. Exp Mol Med. 2021 Feb;53(2):151-167. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. Fu X, Cui J, Meng X, Jiang P, Zheng Q, Zhao W, Chen X. Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review). Oncol Rep. 2021; 45(3): 801-808. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Wu D, Huang LF, Chen XC, Huang XR, Li HY, An N, et al. Research progress on endoplasmic reticulum homeostasis in kidney diseases. Cell Death Dis. 2023; 14(7): 473. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Nakada EM, Sun R, Fujii U, Martin JG. The Impact of Endoplasmic Reticulum-Associated Protein Modifications, Folding and Degradation on Lung Structure and Function. Front Physiol. 2021; 12: 665622. [View at Publisher] [DOI] [PMID] [Google Scholar]
16. Ajoolabady A, Kaplowitz N, Lebeaupin C, Kroemer G, Kaufman RJ, Malhi H, et al. Endoplasmic reticulum stress in liver diseases. Hepatology. 2023; 77(2): 619-639. [View at Publisher] [DOI] [PMID] [Google Scholar]
17. Hou W, Nsengimana B, Yan C, Nashan B, Han S. Involvement of endoplasmic reticulum stress in rifampicin-induced liver injury. Front Pharmacol. 2022; 13: 1022809. [View at Publisher] [DOI] [PMID] [Google Scholar]
18. Rada P, González-Rodríguez Á, García-Monzón C, Valverde ÁM. Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver? Cell Death Dis. 2020; 11(9): 802. [View at Publisher] [DOI] [PMID] [Google Scholar]
19. Zhao J, Hu Y, Peng J. Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): a promising new therapy. Cell Mol Biol Lett. 2021; 26(1): 17. [View at Publisher] [DOI] [PMID] [Google Scholar]
20. Wei J, Fang D. Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma. Int J Mol Sci. 2021; 22(4): 1799. [View at Publisher] [DOI] [PMID] [Google Scholar]
21. Zhao Q, Zhang H, Wu J, Lv X, Jin X, Hu J. Melatonin inhibits the endoplasmic reticulum stress‑induced, C/EBP homologous protein‑mediated pathway in acute pancreatitis. Mol Med Rep. 2020; 22(2): 1647-1655. [View at Publisher] [DOI] [PMID] [Google Scholar]
22. Song MJ, Malhi H. The unfolded protein response and hepatic lipid metabolism in non alcoholic fatty liver disease. Pharmacol Ther. 2019; 203: 107401. [View at Publisher] [DOI] [PMID] [Google Scholar]
23. 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. [View at Publisher] [DOI] [PMID] [Google Scholar]
24. Stefano JT, Duarte SMB, Ribeiro Leite Altikes RG, Oliveira CP. Non-pharmacological management options for MAFLD: a practical guide. Ther Adv Endocrinol Metab. 2023; 14: 20420188231160394. [View at Publisher] [DOI] [PMID] [Google Scholar]
25. Bacchi E, Negri C, Targher G, Faccioli N, Lanza M, Zoppini G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology. 2013; 58(4): 1287-95. [View at Publisher] [DOI] [PMID] [Google Scholar]
26. Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol. 2018; 69(6): 1349-1356. [View at Publisher] [DOI] [PMID] [Google Scholar]
27. Jia Y, Yao Y, Zhuo L, Chen X, Yan C, Ji Y, Tao J, Zhu Y. Aerobic Physical Exercise as a Non-medical Intervention for Brain Dysfunction: State of the Art and Beyond. Front Neurol. 2022; 13: 862078. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Botrus G, Miller RM, Uson Junior PLS, Kannan G, Han H, Von Hoff DD. Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR). Int J Mol Sci. 2022; 24(1): 577. [View at Publisher] [DOI] [PMID] [Google Scholar]
29. Islam MA, Adachi S, Shiiba Y, Takeda KI, Haga S, Yonekura S. Effects of starvation-induced negative energy balance on endoplasmic reticulum stress in the liver of cows. Anim Biosci. 2022; 35(1): 22-28. [View at Publisher] [DOI] [PMID] [Google Scholar]
30. Mansour SZ, Moustafa EM, Moawed FSM. Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats. Cell Stress Chaperones. 2022; 27(5): 499-511. [View at Publisher] [DOI] [PMID] [Google Scholar]
31. Almanza A, Carlesso A, Chintha C, Creedican S, Doultsinos D, Leuzzi B, et al. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. FEBS J. 2019; 286(2): 241-278. [View at Publisher] [DOI] [PMID] [Google Scholar]
32. Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol. 2020; 21(8): 421-438. [View at Publisher] [DOI] [PMID] [Google Scholar]
33. Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, et al. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis. Cell. 2015; 161(7): 1527-38. [View at Publisher] [DOI] [PMID] [Google Scholar]
34. Sung-Min Park, Tae-Il Kang and Jae-Seon So. Roles of XBP1s in Transcriptional Regulation of Target Genes. Biomedicines 2021; 9: 791. [View at Publisher] [DOI] [PMID] [Google Scholar]
35. Petrescu M, Vlaicu SI, Ciumărnean L, Milaciu MV, Mărginean C, Florea M, Vesa ȘC, Popa M. Chronic Inflammation-A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue. Medicina (Kaunas). 2022; 58(5): 641. [View at Publisher] [DOI] [PMID] [Google Scholar]
36. Heinle JW, DiJoseph K, Sabag A, Oh S, Kimball SR, Keating S, Stine JG. Exercise Is Medicine for Nonalcoholic Fatty Liver Disease: Exploration of Putative Mechanisms. Nutrients. 2023; 15(11): 2452. [View at Publisher] [DOI] [PMID] [Google Scholar]
37. Bartoszewska S, Collawn JF. Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia. Cell Mol Biol Lett. 2020; 25: 18. [View at Publisher] [DOI] [PMID] [Google Scholar]
38. Alex S, Boss A, Heerschap A, Kersten S. Exercise training improves liver steatosis in mice. Nutrition & metabolism. 2015; 12(1): 1-1. [View at Publisher] [DOI] [PMID] [Google Scholar]
39. Jaud M, Philippe C, Di Bella D, Tang W, Pyronnet S, Laurell H, Mazzolini L, Rouault-Pierre K, Touriol C. Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers. Cells. 2020; 9(3): 540. [View at Publisher] [DOI] [PMID] [Google Scholar]
40. Park SM, Kang TI, So JS. Roles of XBP1s in Transcriptional Regulation of Target Genes. Biomedicines. 2021; 9(7): 791. [View at Publisher] [DOI] [PMID] [Google Scholar]
41. Sharma RB, Snyder JT, Alonso LC. Atf6α impacts cell number by influencing survival, death and proliferation. Mol Metab. 2019; 27S(Suppl): S69-S80. [View at Publisher] [DOI] [PMID] [Google Scholar]
42. Zhao P, Huang P, Xu T, Xiang X, Sun Y, Liu J, et al. Fat body Ire1 regulates lipid homeostasis through the Xbp1s-FoxO axis in Drosophila. iScience. 2021; 24(8): 102819. [View at Publisher] [DOI] [PMID] [Google Scholar]
43. Pinto AP, Vieira TS, Marafon BB, Batitucci G, Cabrera EMB, da Rocha AL, et al. The Combination of Fasting, Acute Resistance Exercise, and Protein Ingestion Led to Different Responses of Autophagy Markers in Gastrocnemius and Liver Samples. Nutrients. 2020; 12(3): 641. [View at Publisher] [DOI] [PMID] [Google Scholar]
44. Debnath J, Gammoh N, Ryan KM. Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023; 24(8): 560-575. [View at Publisher] [DOI] [PMID] [Google Scholar]
45. Zou Y, Qi Z. Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways. Mediators Inflamm. 2020; 2020: 6412916. [View at Publisher] [DOI] [PMID] [Google Scholar]
46. Lu X, Ding Y, Liu H, Sun M, Chen C, Yang Y, Wang H. The Role of Hydrogen Sulfide Regulation of Autophagy in Liver Disorders. Int J Mol Sci. 2022; 23(7): 4035. [View at Publisher] [DOI] [PMID] [Google Scholar]
47. Zhang Y, Liu Y, Liu X, Yuan X, Xiang M, Liu J, et al. Exercise and Metformin Intervention Prevents Lipotoxicity-Induced Hepatocyte Apoptosis by Alleviating Oxidative and ER Stress and Activating the AMPK/Nrf2/HO-1 Signaling Pathway in db/db Mice. Oxid Med Cell Longev. 2022; 2022:2297268. [View at Publisher] [DOI] [PMID] [Google Scholar]
48. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with Diet, Physical Activity and Exercise. J Hepatol. 2017; 67: 829-846. [View at Publisher] [DOI] [PMID] [Google Scholar]
49. Cheang WS, Wong WT, Zhao L, Xu J, Wang L, Lau CW, et al. PPARδ Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice. Diabetes. 2017; 66(2): 519-528.17. [View at Publisher] [DOI] [PMID] [Google Scholar]
50. Thomas Marjot ,Jeremy W Tomlinson, Leanne Hodson, David W Ray. Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD. 2023; 72: 1607-1619. [View at Publisher] [DOI] [PMID] [Google Scholar]
51. Askari A, Askari B, Fallah Z, Kazemi Sh . Effect of eight weeks aerobic training on serum lipid and lipoprotein levels in women. J Gorgan Univ Med Sci. 2012; 14 (1) :26-32. [View at Publisher] [Google Scholar]
52. Dadban Shahamat M, askari A, Arab Koohsar R. Effects of Four Weeks of High-Intensity Intermittent Training and Continuous Walking on Atherogenic Indices of Obese Middle-Aged Men. mljgoums 2021; 15 (2) :42-47. [View at Publisher] [DOI] [Google Scholar]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Enamad
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.