تأثیر مداخلة همزمان تمرین هوازی تناوبی و دریافت عصارة کرم آرد بر بیان ژن‌های CHOP و BIP و نشانگرهای فشار اکسایشی MDA و SOD بافت کبد موش‌های صحرایی مبتلا به کبد چرب غیرالکلی

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه فیزیولوژی ورزش، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران

چکیده

زمینه و هدف: تنظیم اتوفاژی، تنش شبکۀ اندوپلاسمی (ER)، فعالیت لیزوزومی و ارتباط آن‌ها با فشار اکسایشی به‌عنوان اهداف زیربنایی یاخته‌ای در درمان کبد چرب غیرالکلی (NAFLD) مطرح شده‌اند. امروزه بررسی تغییرات حاصل از مداخلات درمانی NAFLD به‌ویژه ورزش و اصلاح رژیم غذایی بر برخی نشانگرهای کبدی در اتوفاژی، تنش یاخته‌ای و سوخت‌وساز چربی ضروری به‌نظر می‌رسد. از این‌رو، این پژوهش با هدف بررسی تأثیر مداخلۀ همزمان تمرین هوازی تناوبی و دریافت عصارۀ کرم آرد بر بیان ژن‌های پروتئین ایمونوگلوبولین پیوندی (BIP)، پروتئین همولوگ C/EBP (CHOP)، مالون دی آلدئید (MDA) و سوپراکساید دیسموتاز (SOD) بافت کبد موش‌های صحرایی مبتلا به کبد چرب غیرالکلی انجام گرفت.
مواد و روش‌ها: این پژوهش تجربی و کاربردی، روی 25 سر موش صحرایی نر ویستار انجام شد که به پنج گروه مساوی شامل 1. سالم، 2. بیمار، 3. بیمار+ مکمل، 4. بیمار+ ورزش، 5. بیمار+ مکمل+ ورزش تقسیم شدند. به‌منظور القای NAFLD، نمونه‌ها به مدت 12 هفته با رژیم غذایی پرچرب، کلسترول و اسید کولیک تغذیه شدند و گروه سالم، رژیم غذایی استاندارد جوندگان را دریافت کردند. پس از اطمینان از القای بیماری، تمرین هوازی تناوبی با شدت متوسط، هشت هفته، پنج جلسه در هفته دویدن روی نوار گردان (در مجموع 30 دقیقه) همراه با اضافه بار تدریجی انجام شد. گاواژ مکمل عصارۀ کرم آرد، با دوز 20 میلی‌گرم/کیلوگرم وزن بدن مشابه با روزهای ورزش صورت گرفت. اندازه‌گیری بیان کبدی ژن‌های BIP و CHOP به روش Real-Time PCR و غلظت‌های کبدی MDA و SOD به روش وسترن بلات صورت گرفت. داده‌های حاصل از طریق آزمون‌های آماری t-مستقل و تحلیل واریانس دوعاملی در سطح معناداری 05/0P≤ بررسی شدند.
نتایج: در موش‌های صحرایی با الگوی NAFLD، افزایش سطوح کبدی BIP، CHOP و MDA و کاهش سطح SOD دیده شد. تمرین و دریافت عصارۀ کرم آرد، هر کدام به‌تنهایی و همچنین در تعامل با یکدیگر به کاهش معنادار سطوح BIP، CHOP و MDA و افزایش معنادار SOD در موش‌های مبتلا به NAFLD منجر شدند (01/0P≤)؛ اندازۀ اثر تمرین نسبت به مکمل تنها یا تعامل تمرین و مکمل، فقط در افزایش SOD بالاتر بود.
 نتیجه‌گیری: بر پایۀ یافته‌های پژوهش گمان می‌رود مداخلات همزمان تمرین تناوبی هوازی به‌همراه دریافت عصارۀ کرم آرد از طریق کاهش انباشت چربی کبدی، تنش ER و فشار اکسایشی و نقش آن‌ها در تنظیم اتوفاژی در درمان NAFLD مؤثر باشد. نیاز به پژوهش‌های بیشتر به‌منظور روشن شدن سازوکار اثر این مداخلات پژوهشی بر ژن‌های BIP و CHOP و نقش میانجیگری آن‌ها در تنظیم اتوفاژی و تنش یاخته‌ای احساس می‌شود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of simultaneous intervention of interval aerobic training and mealworm extract on the expression of CHOP and BIP genes and oxidative stress markers of MDA and SOD in liver tissue of rats with non-alcoholic fatty liver disease

نویسندگان [English]

  • Zohreh Bagherpour
  • Alireza Rahimi
  • Fariba Aghaei
  • Foad Feizolahi
Department of exercise physiology, Karaj branch, Islamic Azad University, Karaj, Iran
چکیده [English]

Background and Purpose: Regulation of autophagy, endoplasmic reticulum (ER) stress, lysosomal activity and their relationship with oxidative stress have been proposed as underlying cellular targets in the treatment of non-alcoholic fatty liver disease (NAFLD). Nowadays, it seems necessary to investigate the changes resulting from NAFLD therapeutic interventions, especially exercise and dietary modification, on some hepatic markers in autophagy, cellular stress, and lipid metabolism. Therefore, the aim of this study was to investigate the simultaneous effects of interval aerobic training and mealworm extract on the expression of genes of bound immunoglobulin protein (BIP), C/EBP homolog protein (CHOP), malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissue of rats with nonalcoholic fatty liver.
Materials and Methods: This experimental and applied study was conducted on 25 male Wistar rats, which were divided into five equal groups: 1) healthy, 2) diseased, 3) diseased + supplement, 4) diseased + exercise, 5) diseased + supplement + exercise. To induce NAFLD, the samples were fed a high-fat, cholesterol, and cholic acid diet for 12 weeks, and the healthy group received a standard rodent diet. After ensuring the induction of the disease, a moderate-intensity interval aerobic training protocol was performed, 8 weeks/5 sessions per week of treadmill running for a total of 30 minutes with gradual overload. The Mealworm extract supplement gavage was performed at a dose of 20 mg/kg body weight similar to the exercise days. Hepatic expression of BIP and CHOP genes was measured by Real-Time PCR and hepatic MDA and SOD concentrations were measured by Western blotting. Data were analyzed using independent t-tests and two-way analysis of variance.
Results: Hepatic levels of BIP, CHOP, and MDA were increased and SOD level was significantly decreased in NAFLD group. Exercise and mealworm extract separately and in interaction with each other, resulted in a significant decrease in BIP, CHOP, and MDA levels and a significant increase in SOD in NAFLD rats (p<0.01). The effect size of exercise was higher than that of supplementation alone or the interaction of exercise and supplementation, only for SOD.
Conclusion: Employing aerobic interval training along with mealworm extract intake simultanuously may be effective in the treatment of NAFLD, possibly through reducing hepatic fat accumulation, ER stress, and oxidative stress, and their role in regulating autophagy. Further research is needed to clarify the mechanism of the effect of these interventions on BIP and CHOP genes and their mediating role in regulating autophagy and cellular stress.
 
 

کلیدواژه‌ها [English]

  • Exercise
  • Mealworm
  • C/EBP Homologous protein
  • Superoxide dismutase
  1. Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017;15(1):45. https://doi.org/10.1186/s12916-017-0806-8
  2. Flessa CM, Kyrou I, Nasiri‐Ansari N, Kaltsas G, Kassi E, Randeva HS. Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD). J Cell Biochem. 2022;123(10):1585-606.https://doi.org/10.1186/ar2921 
  3. Shin YJ, Han SH, Kim DS, Lee GH, Yoo WH, Kang YM, et al. Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress. Arthritis Res Ther. 2010;12(1):R19. https://doi.org/10.1186/ar2941
  4. 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. https://doi.org/10.1155/2022/2297268
  5. Tse G, Yan BP, Chan YW, Tian XY, Huang Y. Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis. Front Physiol. 2016;7:313. https://doi.org/10.3389/fphys.2016.00313
  6. Arya A, Azarmehr N, Mansourian M, Doustimotlagh AH. Inactivation of the superoxide dismutase by malondialdehyde in the nonalcoholic fatty liver disease: a combined molecular docking approach to clinical studies. Arch Physiol Biochem. 2021;127(6):557-64. https://doi.org/10.1080/13813455.2019.1659827 
  7. Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J Gastroenterol. 2017;23(36):6549-70. https://doi.org/10.3748/wjg.v23.i36.6549
  8. Passos E, Ascensão A, Martins MJ, Magalhães J. Endoplasmic reticulum stress response in non-alcoholic steatohepatitis: the possible role of physical exercise. Metabolism. 2015;64(7):780-92. https://doi.org/10.1016/j.metabol.2015.02.003 
  9. Kalaki-Jouybari F, Shanaki M, Delfan M, Gorgani-Firouzjae S, Khakdan S. High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats. Arch Physiol Biochem. 2020;126(3):242-9. https://doi.org/10.1080/13813455.2018.1510968 
  10. Hajighasem A, Farzanegi P, Mazaheri Z. Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. Arch Physiol Biochem. 2019;125(2):142-9. https://doi.org/10.1080/13813455.2018.1441872
  11. Smart NA, King N, McFarlane JR, Graham PL, Dieberg G. Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis. Br J Sports Med. 2018;52(13):834-43. https://doi.org/10.1136/bjsports-2016-096197 
  12. Mohammadpour-Asl S, Roshan-Milani B, Roshan-Milani S, Saboory E, Ghobadian B, Chodari L. Endoplasmic reticulum stress PERK-ATF4-CHOP pathway is involved in non-alcoholic fatty liver disease in type 1 diabetic rats: The rescue effect of treatment exercise and insulin-like growth factor I. Heliyon. 2024;10(5):e27225. https://doi.org/10.1016/j.heliyon.2024.e27225
  13. 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. https://doi.org/10.1016/j.nutres.2024.04.002
  14. Gu J, Liang H, Ge X, Xia D, Pan L, Mi H, et al. A study of the potential effect of yellow mealworm (Tenebrio molitor) substitution for fish meal on growth, immune and antioxidant capacity in juvenile largemouth bass (Micropterus salmoides). Fish Shellfish Immunol. 2022;120:214-21. https://doi.org/10.1016/j.fsi.2021.11.024 
  15. Caldas BV, Guimarães VH, Ribeiro GH, dos Santos TA, Nobre DA, de Castro RJ, et al. Effect of dietary supplementation with Tenebrio molitor wholemeal and fermented flour modulating adipose lipogenesis gene expression in obese mice. J Insects Food Feed. 2023;9(5):625-35. https://doi.org/10.3920/jiff2022.0070 
  16. Lee JY, Im AR, Shim KS, Ji KY, Kim KM, Kim YH, et al. Beneficial effects of insect extracts on nonalcoholic fatty liver disease. J Med Food. 2020;23(7):760-71. https://doi.org/10.1089/jmf.2019.4536 
  17. Seo M, Goo TW, Chung MY, Baek M, Hwang JS, Kim MA, et al. Tenebrio molitor larvae inhibit adipogenesis through AMPK and MAPKs signaling in 3T3-L1 adipocytes and obesity in high-fat diet-induced obese mice. Int J Mol Sci. 2017;18(3):518. https://doi.org/10.3390/ijms18030518
  18. Di Mattia C, Battista N, Sacchetti G, Serafini M. Antioxidant activities in vitro of water and liposoluble extracts obtained by different species of edible insects and invertebrates. Front Nutr. 2019;6:106. https://doi.org/10.3389/fnut.2019.00106
  19. D'Antonio V, Serafini M, Battista N. Dietary modulation of oxidative stress from edible insects: A mini-review. Front Nutr. 2021;8:642551. https://doi.org/10.3389/fnut.2021.642551
  20. Li J, Huang L, Xiong W, Qian Y, Song M. Aerobic exercise improves non-alcoholic fatty liver disease by down-regulating the protein expression of the CNPY2-PERK pathway. Biochem Biophys Res Commun. 2022;603:35-40. https://doi.org/10.1016/j.bbrc.2022.03.008
  21. Kim SY, Park JE, Han JS. Tenebrio molitor (mealworm) extract improves insulin sensitivity and alleviates hyperglycemia in C57BL/Ksj-db/db mice. J Life Sci. 2019;29(5):570-9. https://doi.org/10.5352/JLS.2019.29.5.570
  22. Simoes ICM, Karkucinska-Wieckowska A, Janikiewicz J, Szymanska S, Pronicki M, Dobrzyn P, et al. Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response. Antioxidants (Basel). 2020;9(10):995. https://doi.org/10.3390/antiox9100995
  23. Payne CL, Scarborough P, Rayner M, Nonaka K. A systematic review of nutrient composition data available for twelve commercially available edible insects, and comparison with reference values. Trends Food Sci Technol. 2016;47:69-77. https://doi.org/10.1016/j.tifs.2015.10.012
  24. Bozi LH, Jannig PR, Rolim N, Voltarelli VA, Dourado PM, Wisløff U, et al. Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats. J Cell Mol Med. 2016;20(11):2208-12. https://doi.org/10.1111/jcmm.12894 
  25. Guo D, Sun J, Feng S. Comparative analysis of the effects of high-intensity interval training and traditional aerobic training on improving physical fitness and biochemical indicators in patients with non-alcoholic fatty liver disease. J Sports Med Phys Fitness. 2025;65(1):132-9.
    https://doi.org/10.23736/s0022-4707.24.16206-8
  26. Yang R, Wan L, Zhu H, Peng Y. The effect of 12 week-maximum fat oxidation (FATmax) intensity exercise on microvascular function in obese patients with nonalcoholic fatty liver disease and its mechanism. Gen Physiol Biophys. 2023;42(3):251-62. https://doi.org/10.4149/gpb_2023004
  27. Won SM, Cha HU, Yi SS, Kim SJ, Park SK. Tenebrio molitor extracts modulate the response to environmental stressors and extend lifespan in Caenorhabditis elegans. J Med Food. 2016;19(10):938-44. https://doi.org/10.1089/jmf.2016.3729 
  28. Zhu D, Huang X, Tu F, Wang C, Yang F. Preparation, antioxidant activity evaluation, and identification of antioxidant peptide from black soldier fly (Hermetia illucens L.) larvae. J Food Biochem. 2020;44(5):e13186. https://doi.org/10.1111/jfbc.13186
  29. Mudd N, San Martin-Gonzalez F, Ferruzzi M, Liceaga AM. In vivo antioxidant effect of edible cricket (Gryllodes sigillatus) peptides using a Caenorhabditis elegans model. Food Hydrocoll Health. 2022;2:100083. https://doi.org/10.1016/j.fhfh.2022.100083
  30. Zhang Y, Liu XW, Wei J, Liu XJ, Zhang NY, Sheng L. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. J Physiol Biochem. 2022;78(3):641-52. https://doi.org/10.1007/s13105-022-00884-7
  31. Ruan L, Li F, Li S, Zhang M, Wang F, Lv X, et al. Effect of Different Exercise Intensities on Hepatocyte Apoptosis in HFD‐Induced NAFLD in Rats: The Possible Role of Endoplasmic Reticulum Stress through the Regulation of the IRE1/JNK and eIF2α/CHOP Signal Pathways. Oxid Med Cell Longev. 2021;2021:6378568. https://doi.org/10.1155/2021/6378568
  32. Zou Y, Chen Z, Sun C, Yang D, Zhou Z, Peng X, et al. Exercise intervention mitigates pathological liver changes in NAFLD zebrafish by activating SIRT1/AMPK/NRF2 signaling. Int J Mol Sci. 2021;22(20):10940. https://doi.org/10.3390/ijms222010940
  33. Ham JR, Choi RY, Lee Y, Lee MK. Effects of edible insect Tenebrio molitor larva fermentation extract as a substitute protein on hepatosteatogenesis and proteomic changes in obese mice induced by high-fat diet. Int J Mol Sci. 2021;22(7):3615. https://doi.org/10.3390/ijms22073615
  34. Kang Y, Applegate CC, He F, Oba PM, Vieson MD, Sánchez-Sánchez L, et al. Yellow mealworm (Tenebrio molitor) and lesser mealworm (Alphitobius diaperinus) proteins slowed weight gain and improved metabolism of diet-induced obesity mice. J Nutr. 2023;153(8):2237-48. https://doi.org/10.1016/j.tjnut.2023.06.014 
  35. Liu D, Ma Z, Xu L, Zhang X, Qiao S, Yuan J. PGC1α activation by pterostilbene ameliorates acute doxorubicin cardiotoxicity by reducing oxidative stress via enhancing AMPK and SIRT1 cascades. Aging (Albany NY). 2019;11(22):10061-73. https://doi.org/10.18632/aging.102418
  36. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. J Appl Physiol. 2009;106(3):929-34. https://doi.org/10.1152/japplphysiol.90880.2008

 

  • تاریخ دریافت: 28 فروردین 1404
  • تاریخ بازنگری: 02 خرداد 1404
  • تاریخ پذیرش: 10 تیر 1404
  • تاریخ اولین انتشار: 10 تیر 1404
  • تاریخ انتشار: 01 فروردین 1405