اثر محافظتی تمرین هوازی و ژل رویال بر شاخص‌های پروفیبروژنیک بافت کبدی و مقاومت به انسولین در موش‌های چاق
محورهای موضوعی : تغذیه
علی اصغر علی اصغر معقولی
1
(گروه فیزیولوژی ورزشی واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران)
احمد عبدی
2
(گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران.)
آسیه عباسی دلویی
3
(گروه فیزیولوژی ورزشی، واحد آیت‌الله آملی، دانشگاه آزاد اسلامی، آمل، ایران)
کلید واژه: Smad3, تمرین هوازی, چاقی, ژل رویال, TGF-β,
چکیده مقاله :
مقدمه: چاقی با عوارض متابولیکی متعدد مانند افزایش شاخص‌های پروفیبروژنیک بافت کبدی مشخص می شود. اکثر داروهای ضد چاقی دارای عوارض جانبی کبدی هستند. هدف این پژوهش تعیین اثر محافظتی تمرین هوازی و ژل رویال بر شاخص‌های پروفیبروژنیک بافت کبدی و مقاومت به انسولین در موش‌های چاق بود. مواد و روش‌ها: در این تحقیق تجربی، 45 سر موش صحرایی نر نژاد ویستار در پنج گروه رژیم غذایی نرمال (ND)، رژیم غذایی پرچرب (HFD)، رژیم غذایی پرچرب-تمرین (HFDT)، رژیم غذایی پرچرب-ژل رویال (HFDRJ) و رژیم غذایی پرچرب-تمرین- ژل رویال (HFDTRJ) قرار گرفتند. گروه‌های مکمل، طی دوره مداخله روزانه 100 میلی‌گرم ژل رویال (به ازای هر کیلوگرم وزن بدن) رقیق شده در آب مقطر را به صورت خوراکی دریافت کردند. برنامه تمرین هوازی شامل دویدن روی تردمیل با شدت 60-50 درصد اکسیژن مصرفی (VO2max)، پنج روز هفته به مدت هشت هفته اجرا شد. میزان بیان ژن‌های فاکتور رشدی تغییر شکل دهنده بتا (TGF-β) و Smad3 به روش Real Time PCR اندازه‌گیری شد. یافته‌ها: افزایش معنی‌داری در میزان TGF-β، Smad3 و مقاومت به انسولین در گروه‌های HFD، HFDT، HFDRJ و HFDTRJ نسبت به گروه ND مشاهده شد (001/0=P). همچنین کاهش معنی‌داری در مقادیر TGF-β، Smad3 و مقاومت به انسولین در گروه‌های HFDT، HFDRJ و HFDTRJ نسبت به گروه HFD؛ و HFDTRJ نسبت به گروه‌های HFDRJ مشاهده شد (001/0=P). نتیجه‌گیری: به‌نظر می‌رسد تمرین هوازی به همراه ژل رویال می‌تواند به کاهش مقاومت به انسولین و بهبود شاخص‌های پروفیبروژنیک بافت کبدی در چاقی ناشی از رژیم غذایی پرچرب کمک کند.
Introduction: Obesity is characterized by several metabolic complications such as increased profibrogenic parameters of liver tissue. Most anti-obesity drugs have liver side effects. The aim of this study was to investigate the protective effect of aerobic training and royal jelly on profibrogenic parameters of liver tissue and insulin resistance in obese rats.Materials and Methods: In this experimental study, 45 male Wistar rats were divided into 5 groups: normal diet (ND), high fat diet (HFD), high fat diet - training (HFDT), high fat diet - royal jelly (HFDRJ) and high fat diet - training - royal jelly (HFDTRJ). The supplement groups received 100 mg of royal jelly (per kg of body weight) diluted in distilled water orally during the intervention period. Aerobic training program including running on treadmill with intensity of 50-60% VO2max was performed 5 days week for eight weeks. The genes expression of Transforming Growth Factor β (TGF-β) and Smad3 were measured by Real Time PCR. Results: There was significant increase of TGF-β, Smad3 and insulin resistance in HFD, HFDT, HFDRJ and HFDTRJ groups compared to ND group (P=0.001). Also, there was a significant decrease of TGF-β, Smad3 and insulin resistance in HFDT, HFDRJ and HFDTRJ groups compared to HFD group; and HFDTRJ compared to HFDRJ groups (P=0.001).Conclusion: It seems that the aerobic training with royal jelly can help to decrease of insulin resistance and improve the profibrogenic parameters of liver tissue in obesity caused by high-fat diet.
Bellicha, A., Van Baak, M. A., Battista, F., Beaulieu, K., Blundell, J. E., Busetto, L., Carraça, E. V., Dicker, D., Encantado, J., Ermolao, A., Farpour-Lambert, N., Pramono, A., Woodward, E. & Oppert, J. M. (2021). Effect of exercise training on weight loss, body composition changes, and weight maintenance in adults with overweight or obesity: An overview of 12 systematic reviews and 149 studies. Obesity reviews: an official journal of the International Association for the Study of Obesity, 22 (Suppl 4), e13256.
Cayón, A., Crespo, J., Mayorga, M., Guerra, A. & Pons-Romero, F. (2006). Increased expression of Ob-Rb and its relationship with the overexpression of TGF-beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis. Liver international: official journal of the International Association for the Study of the Liver, 26(9), 1065–1071.
Cullen, J. M. & Stalker, M. J. (2016). Liver and Biliary System. Jubb, Kennedy & Palmer's Pathology of Domestic Animals: Volume 2, 258–352.e1.
Dooley, S. & Ten Dijke, P. (2012). TGF-β in progression of liver disease. Cell and tissue research, 347(1), 245–256.
Dooley, S., Weng, H. & Mertens, P. R. (2009). Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Digestive diseases (Basel, Switzerland), 27(2), 93–101.
El-Nekeety, A. A., El-Kholy, W., Abbas, N. F., Ebaid, A., Amra, H. A. & Abdel-Wahhab, M. A. (2007). Efficacy of royal jelly against the oxidative stress of fumonisin in rats. Toxicon: official journal of the International Society on Toxicology, 50(2), 256–269.
Glass, D. J. (2010). Signaling pathways perturbing muscle mass. Current opinion in clinical nutrition and metabolic care, 13(3), 225–229.
Gregory, J. W. (2019). Prevention of Obesity and Metabolic Syndrome in Children. Frontiers in endocrinology, 10, 669.
Gressner, A. M., Weiskirchen, R., Breitkopf, K. & Dooley, S. (2002). Roles of TGF-beta in hepatic fibrosis. Frontiers in bioscience: a journal and virtual library, 7, d793–d807.
Habibian, M. & Asadi, M. A. (2015). The Combined Effects of Regular Swimming Exercise and Garlic Extract on the some of the Mediator Growth Factors on the Cardiac Angiogenesis and Fibrosis in aged Rats. jmj. 13 (4) :39-46
Derosa, G. & Maffioli, P. (2012). Anti-obesity drugs: a review about their effects and their safety. Expert opinion on drug safety, 11(3), 459–471.
Karadeniz, A., Simsek, N., Karakus, E., Yildirim, S., Kara, A., Can, I., Kisa, F., Emre, H. & Turkeli, M. (2011). Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin. Oxidative medicine and cellular longevity, 2011, 981793.
Khazaei, M., Ansarian, A. & Ghanbari, E. (2018). New findings on biological actions and clinical applications of Royal Jelly: a review. Journal of Dietary Supplements, 15(5), 757–75.
Kim, Y. J., Hwang, S. J., Bae, Y. C. & Jung, J. S. (2009). MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem cells (Dayton, Ohio), 27(12), 3093–3102.
Luedde, T., Kaplowitz, N. & Schwabe, R. F. (2014). Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology, 147(4), 765–783.e4.
Marra, F., Gastaldelli, A., Svegliati Baroni, G., Tell, G. & Tiribelli, C. (2008). Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends in molecular medicine, 14(2), 72–81.
Mesri Alamdari, N., Irandoost, P., Roshanravan, N., Vafa, M., Asghari Jafarabadi., M. & Alipour, S. (2020). Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity. Nutrition & Metabolism, 17, 1-13.
Moghadam, V., Piri, M., Azarbayjani, M. A. & Matin Homaee, H. (2017). The protective effect of aerobic exercise on breast cancer by TGFβ protein and Smad-3 and MMP2 gene in female mice. SJKU. 22 (3), 60-73
Nagai, T. & Inoue, R. (2008). Preparation and the functional properties of water extract and alkaline extract of royal jelly. Food Chemistry, 84(2), 181-186.
Omer, K., Gelkopf, M. J. & Newton, G. (2019). Effectiveness of royal jelly supplementation in glycemic regulation: A systematic review. World journal of diabetes, 10(2), 96–113.
Oppert, J. M., Bellicha, A., Van Baak, M. A., Battista, F., Beaulieu, K., Blundell, J. E., Carraça, E. V., Encantado, J., Ermolao, A., Pramono, A., Farpour-Lambert, N., Woodward, E., Dicker, D. & Busetto, L. (2021). Exercise training in the management of overweight and obesity in adults: Synthesis of the evidence and recommendations from the European Association for the Study of Obesity Physical Activity Working Group. Obesity reviews: an official journal of the International Association for the Study of Obesity, 22 (Suppl 4), e13273.
Rocha-Rodrigues, S., Rodríguez, A., Gouveia, A. M., Gonçalves, I. O., Becerril, S., Ramírez, B., Beleza, J., Frühbeck, G., Ascensão, A. & Magalhães, J. (2016). Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life sciences, 165, 100–108.
Sajadian, S. & Nikooie, R. (2014). TGF-β1 protein Expression in the Skeletal Muscle Following High Interval Training and its Relationship with Intramuscular Triglycerides Oxidation. Journal of Sport in Biomotor Sciences, 6, 2.
Selman, M., King, T. E. & Pardo, A. (2001). American Thoracic Society, European Respiratory Society, & American College of Chest Physicians. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Annals of internal medicine, 134(2), 136–151.
Shalizar Jalali, A., Najafi, G, Hosseinchi, M. & Sedighnia, A. (2015). Royal jelly alleviates sperm toxicity and improves in vitro fertilization outcome in Stanozolol-treated mice. Iranian Journal of Reproductive Medicine, 13(1), 15-22.
Silici, S., Ekmekcioglu, O., Kanbur, M. & Deniz, K. (2011). The protective effect of royal jelly against cisplatin-induced renal oxidative stress in rats. World journal of urology, 29(1), 127–132.
Takikawa, M., Kumagai, A., Hirata, H., Soga, M., Yamashita, Y., Ueda, M., Ashida, H. & Tsuda, T. (2013). 10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid, activates 5'-AMP-activated protein kinase in L6 myotubes and mice. Molecular nutrition & food research, 57(10), 1794–1802.
Tan, C. K., Leuenberger, N., Tan, M. J., Yan, Y. W., Chen, Y., Kambadur, R., Wahli, W. & Tan, N. S. (2011). Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet. Diabetes, 60(2), 464–476.
Terada, Y., Narukawa, M. & Watanabe, T. (2011). Specific hydroxy fatty acids in royal jelly activate TRPA1. Journal of agricultural and food chemistry, 59(6), 2627–2635.
Torok, N. J. (2016). Dysregulation of redox pathways in liver fibrosis. American journal of physiology. Gastrointestinal and liver physiology, 311(4), G667–G674.
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., Sun, P., Lonning, S., Skarulis, M., Sumner, A. E., Finkel, T. & Rane, S. G. (2011). Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell metabolism, 14(1), 67–79.
Yamada, H., Iwaki, Y., Kitaoka, R., Fujitani, M., Shibakusa, T., Fujikawa, T., Matsumura, S., Fushiki, T. & Inoue, K. (2012). Blood lactate functions as a signal for enhancing fatty acid metabolism during exercise via TGF-β in the brain. Journal of nutritional science and vitaminology, 58(2), 88–95.
Yang, L., Roh, Y. S., Song, J., Zhang, B., Liu, C., Loomba, R. & Seki, E. (2014). Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology (Baltimore, Md.), 59(2), 483–495.
Yoneshiro, T., Kaede, R., Nagaya, K., Aoyama, J., Saito, M., Okamatsu-Ogura, Y., Kimura, K. & Terao, A. (2018). Royal jelly ameliorates diet-induced obesity and glucose intolerance by promoting brown adipose tissue thermogenesis in mice. Obesity research & clinical practice, 12(Suppl 2), 127–137.
Zhang, F., Ni, C., Kong, D., Zhang, X., Zhu, X., Chen, L., Lu, Y. & Zheng, S. (2012). Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways. Toxicology and applied pharmacology, 265(1), 51–60.
_||_Bellicha, A., Van Baak, M. A., Battista, F., Beaulieu, K., Blundell, J. E., Busetto, L., Carraça, E. V., Dicker, D., Encantado, J., Ermolao, A., Farpour-Lambert, N., Pramono, A., Woodward, E. & Oppert, J. M. (2021). Effect of exercise training on weight loss, body composition changes, and weight maintenance in adults with overweight or obesity: An overview of 12 systematic reviews and 149 studies. Obesity reviews: an official journal of the International Association for the Study of Obesity, 22 (Suppl 4), e13256.
Cayón, A., Crespo, J., Mayorga, M., Guerra, A. & Pons-Romero, F. (2006). Increased expression of Ob-Rb and its relationship with the overexpression of TGF-beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis. Liver international: official journal of the International Association for the Study of the Liver, 26(9), 1065–1071.
Cullen, J. M. & Stalker, M. J. (2016). Liver and Biliary System. Jubb, Kennedy & Palmer's Pathology of Domestic Animals: Volume 2, 258–352.e1.
Dooley, S. & Ten Dijke, P. (2012). TGF-β in progression of liver disease. Cell and tissue research, 347(1), 245–256.
Dooley, S., Weng, H. & Mertens, P. R. (2009). Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Digestive diseases (Basel, Switzerland), 27(2), 93–101.
El-Nekeety, A. A., El-Kholy, W., Abbas, N. F., Ebaid, A., Amra, H. A. & Abdel-Wahhab, M. A. (2007). Efficacy of royal jelly against the oxidative stress of fumonisin in rats. Toxicon: official journal of the International Society on Toxicology, 50(2), 256–269.
Glass, D. J. (2010). Signaling pathways perturbing muscle mass. Current opinion in clinical nutrition and metabolic care, 13(3), 225–229.
Gregory, J. W. (2019). Prevention of Obesity and Metabolic Syndrome in Children. Frontiers in endocrinology, 10, 669.
Gressner, A. M., Weiskirchen, R., Breitkopf, K. & Dooley, S. (2002). Roles of TGF-beta in hepatic fibrosis. Frontiers in bioscience: a journal and virtual library, 7, d793–d807.
Habibian, M. & Asadi, M. A. (2015). The Combined Effects of Regular Swimming Exercise and Garlic Extract on the some of the Mediator Growth Factors on the Cardiac Angiogenesis and Fibrosis in aged Rats. jmj. 13 (4) :39-46
Derosa, G. & Maffioli, P. (2012). Anti-obesity drugs: a review about their effects and their safety. Expert opinion on drug safety, 11(3), 459–471.
Karadeniz, A., Simsek, N., Karakus, E., Yildirim, S., Kara, A., Can, I., Kisa, F., Emre, H. & Turkeli, M. (2011). Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin. Oxidative medicine and cellular longevity, 2011, 981793.
Khazaei, M., Ansarian, A. & Ghanbari, E. (2018). New findings on biological actions and clinical applications of Royal Jelly: a review. Journal of Dietary Supplements, 15(5), 757–75.
Kim, Y. J., Hwang, S. J., Bae, Y. C. & Jung, J. S. (2009). MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem cells (Dayton, Ohio), 27(12), 3093–3102.
Luedde, T., Kaplowitz, N. & Schwabe, R. F. (2014). Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology, 147(4), 765–783.e4.
Marra, F., Gastaldelli, A., Svegliati Baroni, G., Tell, G. & Tiribelli, C. (2008). Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends in molecular medicine, 14(2), 72–81.
Mesri Alamdari, N., Irandoost, P., Roshanravan, N., Vafa, M., Asghari Jafarabadi., M. & Alipour, S. (2020). Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity. Nutrition & Metabolism, 17, 1-13.
Moghadam, V., Piri, M., Azarbayjani, M. A. & Matin Homaee, H. (2017). The protective effect of aerobic exercise on breast cancer by TGFβ protein and Smad-3 and MMP2 gene in female mice. SJKU. 22 (3), 60-73
Nagai, T. & Inoue, R. (2008). Preparation and the functional properties of water extract and alkaline extract of royal jelly. Food Chemistry, 84(2), 181-186.
Omer, K., Gelkopf, M. J. & Newton, G. (2019). Effectiveness of royal jelly supplementation in glycemic regulation: A systematic review. World journal of diabetes, 10(2), 96–113.
Oppert, J. M., Bellicha, A., Van Baak, M. A., Battista, F., Beaulieu, K., Blundell, J. E., Carraça, E. V., Encantado, J., Ermolao, A., Pramono, A., Farpour-Lambert, N., Woodward, E., Dicker, D. & Busetto, L. (2021). Exercise training in the management of overweight and obesity in adults: Synthesis of the evidence and recommendations from the European Association for the Study of Obesity Physical Activity Working Group. Obesity reviews: an official journal of the International Association for the Study of Obesity, 22 (Suppl 4), e13273.
Rocha-Rodrigues, S., Rodríguez, A., Gouveia, A. M., Gonçalves, I. O., Becerril, S., Ramírez, B., Beleza, J., Frühbeck, G., Ascensão, A. & Magalhães, J. (2016). Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life sciences, 165, 100–108.
Sajadian, S. & Nikooie, R. (2014). TGF-β1 protein Expression in the Skeletal Muscle Following High Interval Training and its Relationship with Intramuscular Triglycerides Oxidation. Journal of Sport in Biomotor Sciences, 6, 2.
Selman, M., King, T. E. & Pardo, A. (2001). American Thoracic Society, European Respiratory Society, & American College of Chest Physicians. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Annals of internal medicine, 134(2), 136–151.
Shalizar Jalali, A., Najafi, G, Hosseinchi, M. & Sedighnia, A. (2015). Royal jelly alleviates sperm toxicity and improves in vitro fertilization outcome in Stanozolol-treated mice. Iranian Journal of Reproductive Medicine, 13(1), 15-22.
Silici, S., Ekmekcioglu, O., Kanbur, M. & Deniz, K. (2011). The protective effect of royal jelly against cisplatin-induced renal oxidative stress in rats. World journal of urology, 29(1), 127–132.
Takikawa, M., Kumagai, A., Hirata, H., Soga, M., Yamashita, Y., Ueda, M., Ashida, H. & Tsuda, T. (2013). 10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid, activates 5'-AMP-activated protein kinase in L6 myotubes and mice. Molecular nutrition & food research, 57(10), 1794–1802.
Tan, C. K., Leuenberger, N., Tan, M. J., Yan, Y. W., Chen, Y., Kambadur, R., Wahli, W. & Tan, N. S. (2011). Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet. Diabetes, 60(2), 464–476.
Terada, Y., Narukawa, M. & Watanabe, T. (2011). Specific hydroxy fatty acids in royal jelly activate TRPA1. Journal of agricultural and food chemistry, 59(6), 2627–2635.
Torok, N. J. (2016). Dysregulation of redox pathways in liver fibrosis. American journal of physiology. Gastrointestinal and liver physiology, 311(4), G667–G674.
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., Sun, P., Lonning, S., Skarulis, M., Sumner, A. E., Finkel, T. & Rane, S. G. (2011). Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell metabolism, 14(1), 67–79.
Yamada, H., Iwaki, Y., Kitaoka, R., Fujitani, M., Shibakusa, T., Fujikawa, T., Matsumura, S., Fushiki, T. & Inoue, K. (2012). Blood lactate functions as a signal for enhancing fatty acid metabolism during exercise via TGF-β in the brain. Journal of nutritional science and vitaminology, 58(2), 88–95.
Yang, L., Roh, Y. S., Song, J., Zhang, B., Liu, C., Loomba, R. & Seki, E. (2014). Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology (Baltimore, Md.), 59(2), 483–495.
Yoneshiro, T., Kaede, R., Nagaya, K., Aoyama, J., Saito, M., Okamatsu-Ogura, Y., Kimura, K. & Terao, A. (2018). Royal jelly ameliorates diet-induced obesity and glucose intolerance by promoting brown adipose tissue thermogenesis in mice. Obesity research & clinical practice, 12(Suppl 2), 127–137.
Zhang, F., Ni, C., Kong, D., Zhang, X., Zhu, X., Chen, L., Lu, Y. & Zheng, S. (2012). Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways. Toxicology and applied pharmacology, 265(1), 51–60.