تأثیر هشت هفته تمرین تناوبی شنا با شدت بالا بر بیان پروتئین RBP4 کبد، hs-CRP سرم و مقاومت به انسولین در موش‌های صحرایی مبتلا به استئاتوهپاتیت غیرالکلی ناشی از مصرف رژیم پرچرب

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه علوم ورزشی، دانشکدة علوم انسانی، دانشگاه هرمزگان، بندرعباس، ایران

2 گروه علوم ورزشی، دانشکده علوم تربیتی و روانشناسی، دانشگاه شیراز، شیراز، ایران

چکیده

زمینه و هدف: بیماری استئاتوهپاتیت غیرالکلی (NASH) یک چالش مهم بهداشت همگانی است و پروتئین اتصال رتینول 4 (RBP4) وابستگی نزدیکی با این بیماری دارد. RBP4 تنها پروتئین ناقل خاص شناخته‌شده برای ویتامین A است که سطوح در گردش رتینول به‌عنوان یک ضداکساینده را تنظیم می‌کند. بافت کبد تولیدکنندة اصلی RBP4 است و می‌تواند به هومئوستاز رتینوئیدی کل بدن کمک کند. تجمع تری‌گلیسیرید، افزایش سطح التهاب و فشار اکسایشی را در پی دارد و در پاسخ به این تغییر، شاید سطح RBP4 و نشانگرهای التهابی از جمله پروتئین واکنشی C با حساسیت بالا (hs-CRP) دستخوش تغییر شود. بدین‌ترتیب گمان می‌رود که با پیشرفت بیماری و افزایش سطح فشار اکسایشی و التهاب، نشانگرهای پاسخ‌دهنده به آن‌ها از جمله RBP4 و hs-CRP نیز دچار تغییر شوند. بنابراین پژوهش حاضر با هدف بررسی تأثیر هشت هفته تمرین تناوبی شنا با شدت بالا بر بیان پروتئین RBP4 کبد، CRP سرم و سطح مقاومت به انسولین در موش‌های صحرایی مبتلا به استئاتوهپاتیت غیرالکلی ناشی از مصرف رژیم پرچرب انجام گرفت.
مواد و روش‌ها: 40 سر موش صحرایی نر (سن شش تا هشت هفته، وزن 20±230 گرم، نژاد Sprague – Dawley) در چهار گروه کنترل- NASH (9= n)، تمرین-NASH (9= n)، کنترل-سالم (9= n) و تمرین-سالم (9= n) جایگزین شدند. HIIT شنا، شامل 20 نوبت 30 ثانیه‌ای شنا با 30 ثانیه استراحت بین هر نوبت (هشت هفته، سه روز در هفته، روزهای زوج) بود. در پایان دوره تمرینی پروتئین RBP4 درون‌کبدی از شیوة وسترن بلات و hs-CRP، انسولین و قند خون ناشتای سرم از روش الایزا و فتومتریک اندازه‌گیری شد. برای تعیین تفاوت میان گروه‌ها از آزمون آنووای یکراهه و برای تعیین تفاوت درون‌گروهی از آزمون تعقیبی بانفرونی با استفاده از نرم‌افزار SPSS26، استفاده شد و سطح معناداری 05/0P< در نظر گرفته شد.
نتایج: افزایش معنادار پروتئین RBP4 در گروه کنترل- NASHدر مقایسه با کنترل-سالم (004/0P=) و کاهش غیرمعنادار RBP4 (762/0P=) و مقاومت به انسولین (14/0P=) در گروه تمرین- NASHدر مقایسه با گروه کنترل- NASHوجود داشت. همچنین کاهش معنادار hs-CRP (007/0P=) و قند خون ناشتا (001/0P=) در گروه تمرین- NASHنسبت به کنترل- NASHدیده شد.
نتیجه‌گیری: تمرینات شنای تناوبی با شدت بالا، می‌تواند التهاب عمومی و سراسری را در بیماری استئاتوهپاتیت غیرالکلی کاهش دهد. بنابراین گمان می‌رود این نوع فعالیت ورزشی جدید بتواند از پیشرفت این بیماری از طریق کنترل پروتئین RBP4 درون‌کبدی و مقاومت به انسولین جلوگیری کند. ازاین‌رو این نوع روش تمرین می‌تواند در بهبود NASH مفید باشد. با این همه تا اثبات کامل، به پژوهش‌های بیشتری در این زمینه نیاز است.
 

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The effect of eight weeks of high-intensity interval swimming training on the expression of liver RBP4 protein, serum hs-CRP and insulin resistance in rats with Non-Alcoholic Steatohepatitis caused by consumption of high-fat diet

نویسندگان [English]

  • Mohammad Amin Delavari 1
  • Elham Shahabpour 1
  • Alireza Jowhari 2
1 Department of Sports Sciences, Faculty of Humanities, University of Hormozgan, Bandar Abbas, Iran
2 Department of Sports Sciences, Faculty of Psychology and Educational Sciences, Shiraz University, Shiraz, Iran
چکیده [English]

Background and Purpose: Nonalcoholic steatohepatitis (NASH) is an important public health problem, and Retinol-Binding Protein 4 (RBP4) is closely related to this disease. RBP4 is the only known specific transporter protein for vitamin A that regulates circulating levels of retinol as an antioxidant. Liver tissue is the main producer of RBP4 and can contribute to whole body retinoid homeostasis. The accumulation of triglycerides leads to an increase in the level of inflammation and oxidative stress, and in response to this change, the level of RBP4 and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) may change. Thus, it is possible that with the progress of the disease and the increase in the level of oxidative stress and inflammation, the markers that respond to them, including RBP4 and hs-CRP, will also change. Therefore, the aim of this study was to investigate the effect of eight weeks of high-intensity interval swimming training on liver RBP4 protein expression, serum CRP and insulin resistance level in rats suffering from non-alcoholic steatohepatitis caused by consumption of high-fat diet.
Materials and Methods: Forty male Sprague-Dawley rats (Mean±SD; age, 6 to 8 weeks; weight 230±20 grams) were divided into four groups of control-NASH (n=9), exercise-NASH (n=9), control-healthy (9 = n) and exercise-healthy (n = 9). HIIT swimming included 20 repetitions of 30 s swimming with 30 s rest between repetitions (eight weeks, three days a week, on the even days). After the training period, intrahepatic RBP4 protein was measured by western blot technique and hs-CRP, insulin and fasting blood sugar were measured by ELISA and photometric methods. One-way ANOVA test was used to determine between-group differences and Bonferroni's post-hoc test was used to identify which mean differences were statistically significant.
Results: There was a significant increase of RBP4 in the control-NASH group compared to the healthy control (P=0.004) and a non-significant decrease in RBP4 (P=0.762) and insulin resistance (P=0.14) in exercise-NASH compared to the control-NASH. Furthermore, significant decreases in hs-CRP (P=0.007) and fasting blood sugar (P=0.001) were observed in the exercise-NASH group compared to the control-NASH.
Conclusion: Interval high-intensity swimming training can reduce systemic inflammation in non-alcoholic steatohepatitis. Therefore, it seems that this new type of exercise can prevent the progression of this disease through the control of intrahepatic RBP4 protein and insulin resistance. Therefore, this type of exercise protocol can be useful in improving NASH, though, more research is needed in this field to fully prove it.
 
 

کلیدواژه‌ها [English]

  • Non-Alcoholic Steatohepatitis
  • High-Intensity Interval Swimming Training
  • Inflammation
  • Insulin Resistance

مراجع

  1.  

    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nature reviews Gastroenterology & hepatology. 2021 Apr;18(4):223-38. DOI: 10.1038/s41575-020-00381-6
    2. Hu R, Yang X, He X, Song G. The relationship between NAFLD and retinol-binding protein 4-an updated systematic review and meta-analysis. Lipids in Health and Disease. 2023 Jan 21;22(1):8. DOI:10.1186/s12944-022-01771-2
    3. Liu Y, Mu D, Chen H, Li D, Song J, Zhong Y, Xia M. Retinol-binding protein 4 induces hepatic mitochondrial dysfunction and promotes hepatic steatosis. The Journal of Clinical Endocrinology & Metabolism. 2016 Nov 1;101(11):4338-48. DOI: 10.1210/jc.2016-1320
    4. Steinhoff JS, Lass A, Schupp M. Biological functions of RBP4 and its relevance for human diseases. Frontiers in Physiology. 2021 Mar 11;12:659977. DOI: 10.3389/fphys.2021.659977
    5. Chen G. The link between hepatic vitamin A metabolism and nonalcoholic fatty liver disease. Current drug targets. 2015 Nov 1;16(12):1281-92. DOI: 10.2174/1389450116666150325231015
    6. Zou W, Wang Z, Xia J, Yang J. Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study. Reproductive Biology and Endocrinology. 2020 Dec;18:1-7.DOI:10.1186/s12958-020-00670-4
    7. Li J, Huang X, Jiang Y, Luo F, Mao Z. Expression and clinical significance of serum retinol binding protein 4, superoxide dismutase and hypersensitive C-reactive protein in patients with acute ST-segment elevated myocardial infarction. Zhonghua wei Zhong Bing ji jiu yi xue. 2020 Oct 1;32(10):1199-202. DOI: 10.3760/cma.j.cn121430-20200113-00132
    8. Wood AD, Strachan AA, Thies F, Aucott LS, Reid DM, Hardcastle AC, Mavroeidi A, Simpson WG, Duthie GG, Macdonald HM. Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk. British journal of nutrition. 2014 Oct;112(8):1341-52. DOI: 10.1017/S0007114514001962
    9. De Dios O, Navarro P, Ortega-Senovilla H, Herrero L, Gavela-Pérez T, Soriano-Guillen L, Lasunción MA, Garcés C. Plasma retinol levels and high-sensitivity C-reactive protein in prepubertal children. Nutrients. 2018 Sep 7;10(9):1257. DOI: 10.3390/nu10091257
    10. Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The liver as an endocrine organ—linking NAFLD and insulin resistance. Endocrine reviews. 2019 Oct;40(5):1367-93. DOI: 10.1210/er.2019-00034
    11. Kataria Y, Deaton RJ, Enk E, Jin M, Petrauskaite M, Dong L, Goldenberg JR, Cotler SJ, Jensen DM, Van Breemen RB, Gann PH. Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer. BMC gastroenterology. 2016 Dec;16:1-2. DOI: 10.1186/s12876-016-0432-5
    12. 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. Archives of physiology and biochemistry. 2020 May 26;126(3):242-9. DOI: 10.1080/13813455.2018.1510968
    13. Khalafi M, Symonds ME. The impact of high intensity interval training on liver fat content in overweight or obese adults: A meta-analysis. Physiology & Behavior. 2021 Jul 1;236:113416. DOI: 10.1016/j.physbeh.2021.113416
    14. Khalafi M, Symonds ME. The impact of high intensity interval training on liver fat content in overweight or obese adults: A meta-analysis. Physiology & Behavior. 2021 Jul 1;236:113416. DOI: 10.1111/jdi.12186
    15. Gorbanian B, Saberi Y. Changes in Fetuin-B and RBP4 During A Course of High-Intensity Interval Training in Women with Nonalcoholic Fatty Liver. Journal of Babol University of Medical Sciences. 2021 Jan 1;23(1). DOI: 10.22088/jbums.23.1.398
    16. Phillips A, Cobbold C. A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein‐4. International journal of chronic diseases. 2014;2014(1):358058. DOI: 10.1155/2014/358058
    17. Ghorbanian B, Wong A, Iranpour A. The effect of dietary carbohydrate restriction and aerobic exercise on retinol binding protein 4 (RBP4) and fatty acid binding protein 5 (FABP5) in middle-aged men with metabolic syndrome. British Journal of Nutrition. 2023 Aug;130(4):553-63.DOI:10.1017/S0007114522003580
    18. Naghizadeh H, Heydari F. The effect of 12 weeks of high-intensity interval training and curcumin consumption on plasma levels of IL-6, TNF-alpha and CRP in men with type II diabetes along with hyperlipidemia. Journal of Practical Studies of Biosciences in Sport. 2023 Mar 21;11(25):22-36. DOI:10.22077/jpsbs.2022.4895.1682
    19. Zolfi H, Shakib A, Valipour A. The effect of eight weeks of high-intensity interval training (HIIT) on mir-27a levels and serum c-reactive protein (CRP) concentration in middle-aged obese men. Daneshvar Medicine. 2022 Oct 23;30(4):36-47. DOI:10.22070/daneshmed.2022.16187.1205
    20. Wang S, Zhou H, Zhao C, He H. Effect of exercise training on body composition and inflammatory cytokine levels in overweight and obese individuals: a systematic review and network meta-analysis. Frontiers in immunology. 2022 Jun 23;13:921085. DOI: 10.3389/fimmu.2022.921085
    21. Zou Y, Li J, Lu C, Wang J, Ge J, Huang Y, Zhang L, Wang Y. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life sciences. 2006 Aug 8;79(11):1100-7. DOI: 10.1016/j.lfs.2006.03.021
    22. Chen B, Ma Y, Xue X, Wei J, Hu G, Lin Y. Tetramethylpyrazine reduces inflammation in the livers of mice fed a high fat diet. Molecular Medicine Reports. 2019 Apr 1;19(4):2561-8. DOI: 10.3892/mmr.2019.9928
    23. Jowhari A, Daryanoosh F, Jahromi MK, Nekooeian AA. Effect of High-intensity Intermittent Swimming Training on peroxisome proliferator-activated receptors-αand Liver Enzymes in Non-alcoholic Steatohepatitis Male Rats. Journal of Shahid Sadoughi University of Medical Sciences. 2022 Dec 25.DOI:10.18502/ssu.v30i10.11454
    24. Farzanegi P, Habibian M, Alinejad H. The combined effect of regular aerobic exercise with garlic extract on renal apoptosis regulatory factors in aged rats with chronic kidney disease. Arak Medical University Journal. 2016 Jan 1;19(3):62-70.[In Persian].
    25. Ramos-Filho D, Chicaybam G, de-Souza-Ferreira E, Guerra Martinez C, Kurtenbach E, Casimiro-Lopes G, Galina A. High intensity interval training (HIIT) induces specific changes in respiration and electron leakage in the mitochondria of different rat skeletal muscles. PloS one. 2015 Jun 29;10(6):e0131766. DOI: 10.1371/journal.pone.0131766
    26. Shafiee A, Gaeini A, Soleimani M, Nekouei A, Hadidi V. The effect of eight week of high intensity interval training on expression of mir-210 and ephrinA3 mRNA in soleus muscle healthy male rats. Journal of Arak University of Medical Sciences. 2014 Jun 10;17(3):26-34.[In Persian].
    27. Nankam PA, Blüher M. Retinol-binding protein 4 in obesity and metabolic dysfunctions. Molecular and Cellular Endocrinology. 2021 Jul 1;531:111312. DOI: 10.1016/j.mce.2021.111312
    28. Olsen T, Blomhoff R. Retinol, retinoic acid, and retinol-binding protein 4 are differentially associated with cardiovascular disease, type 2 diabetes, and obesity: an overview of human studies. Advances in Nutrition. 2020 May 1;11(3):644-66. DOI: 10.1093/advances/nmz131
    29. Taghian F. Concurrent exercise and aerobic-resistance exercise ameliorate the serum of Retinol-Binding Protein-4 level and insulin resistance in postmenopausal women. Science & Sports. 2022 Dec 1;37(8):736-44. DOI: 10.1016/j.scispo.2021.06.010
    30. Taghian F, Zolfaghari M, Hedayati M. Effects of aerobic exercise on serum retinol binding protein4, insulin resistance and blood lipids in obese women. Iranian Journal of Public Health. 2014 May;43(5):658. PMID: 26060767
    31. Kurobe K, Kousaka A, Ogita F, Matsumoto N. Metabolic responses to exercise on land and in water following glucose ingestion. Clinical physiology and functional imaging. 2018 Mar;38(2):227-32. DOI: 10.1111/cpf.12404
    32. Lopera CA, da Silva DF, Bianchini JA, Locateli JC, Moreira AC, Dada RP, Thivel D, Junior NN. Effect of water-versus land-based exercise training as a component of a multidisciplinary intervention program for overweight and obese adolescents. Physiology & behavior. 2016 Oct 15;165:365-73. DOI: 10.1016/j.physbeh.2016.08.019
    33. Whillier S. Exercise and insulin resistance. Physical exercise for human health. 2020:137-50. DOI: 10.1007/978-981-15-1792-1_9
    34. Zouhal H, Zare-Kookandeh N, Haghighi MM, Daraei A, de Sousa M, Soltani M, Abderrahman AB, M. Tijani J, Hackney AC, Laher I, Saeidi A. Physical activity and adipokine levels in individuals with type 2 diabetes: A literature review and practical applications. Reviews in Endocrine and Metabolic Disorders. 2021 Dec;22(4):987-1011. DOI: 10.1007/s11154-021-09657-x
    35. Young L. The Influence of Acute and Chronic Exercise on Retinol Binding Protein 4 and Markers of Skeletal Muscle Glucose Uptake (Doctoral dissertation, The University of Utah).
    36. Karamfilova V, Gateva A, Alexiev A, Zheleva N, Velikova T, Ivanova-Boyanova R, Ivanova R, Cherkezov N, Kamenov Z, Mateva L. The association between retinol-binding protein 4 and prediabetes in obese patients with nonalcoholic fatty liver disease. Archives of Physiology and Biochemistry. 2022 Jan 2;128(1):217-22. DOI: 10.1080/13813455.2019.1673429
    37. Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, Ludvik B. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. The Journal of Clinical Endocrinology & Metabolism. 2007 Mar 1;92(3):1168-71. DOI: 10.1210/jc.2006-1839
    38. Fan J, Hu J. Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic β-cell function. Endocrine. 2024 Mar 23:1-5. DOI: 10.1007/s12020-024-03777-5
    39. Zatterale F, Longo M, Naderi J, Raciti GA, Desiderio A, Miele C, Beguinot F. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Frontiers in physiology. 2020 Jan 29;10:1607. DOI: 10.3389/fphys.2019.01607
    40. Sakurai Y, Kubota N, Yamauchi T, Kadowaki T. Role of insulin resistance in MAFLD. International journal of molecular sciences. 2021 Apr 16;22(8):4156. DOI: 10.3390/ijms22084156
    41. Noushad S, Ahmed S, Ansari B, Mustafa UH, Saleem Y, Hazrat H. Physiological biomarkers of chronic stress: A systematic review. International journal of health sciences. 2021 Sep;15(5):46. PMID: 34548863

     

     

     

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  • تاریخ دریافت: 20 خرداد 1403
  • تاریخ بازنگری: 30 مرداد 1403
  • تاریخ پذیرش: 03 شهریور 1403
  • تاریخ اولین انتشار: 03 شهریور 1403
  • تاریخ انتشار: 01 شهریور 1403

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