نوع مقاله : مقاله پژوهشی
نویسندگان
1 کارشناسی ارشد فیزیولوژی ورزش، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه شهید باهنرکرمان، کرمان، ایران.
2 دانشیار گروه فیزیولوژی ورزش، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه شهید باهنرکرمان، کرمان، ایران
3 استادیار گروه فیزیولوژی و فارماکولوژی، دانشکده پزشکی افضلی پور و مرکز تحقیقات فیزیولوژی، انستیتو نوروفارماکولوژی، علوم پزشکی کرمان، کرمان، ایران.
چکیده
زمینه و هدف: رژیم غذایی محدودکننده کالری، یکی از روش های کاهش دریافت کالری بدون سوء تغذیه است. هدف پژوهش حاضر بررسی تاثیر هشت هفته تمرین تناوبی با شدت بالا و رژیم غذایی چرب و یا استاندارد، همراه با محدودیت کالریک، بر بیان ژن های سیرتوئین ۱ (SIRT1)، گیرنده وابسته استروژن آلفا (ERRα) و پیروات دهیدروزناز کینا-۴ (PDK4) در بافت کبد رت های نر نژاد ویستار بود. روش تحقیق: تعداد 48 سر موش صحرایی نر به طور تصادفی به شش گروه (8n=) شامل کنترل، تمرین تناوبی با شدت بالا، رژیم غذایی چرب با محدودیت کالریک، رژیم غذایی استاندارد با محدودیت کالریک، رژیم غذایی استاندارد با محدودیت کالریک + تمرین تناوبی، و رژیم غذایی چرب با محدودیت کالریک + تمرین تناوبی تقسیم شدند. تمرین ورزشی به مدت هشت هفته با تکرار پنج روز در هفته با شدت ۹۰ تا ۱۰۰ درصد سرعت بیشینه به صورت دویدن روی نوارگردان اجرا شد. بیان ژن های SIRT1، ERRα و PDK4 در بافت کبد به روش Real-Time PCR اندازه گیری گردید و از روش آماری تحلیل واریانس یک راهه برای مقایسه بین گروهی در سطح 0/05>p استفاده شد. یافته ها: تمرین تناوبی با شدت بالا، منجر به افزایش معنی دار بیان ژن ERRα نسبت به گروه کنترل شد (0/001=p). رژیم غذایی چرب با محدودیت کالریک، باعث کاهش معنی داری بیان ژن SIRT1 نسبت به رژیم غذایی استاندارد با محدودیت کالریک (0/002=p)؛ و رژیم غذایی استاندارد با محدودیت کالریک، منجر به افزایش معنی داری بیان ژن PDK4 نسبت به گروه کنترل شد (0/02=p). نتیجه گیری: در شرایط محدودیت کالریک، تمرین تناوبی با شدت بالا از طریق بیش تنظیمی بیان ژن ERRα می تواند نقش کلیدی در افزایش گلوکونئوژنز کبدی داشته باشد. به طور جالب، رژیم غذایی پر چرب ممکن است حتی در شرایط محدودیت کالریک، با کاهش بیان SIRT1 - که نقش مهمی در ظرفیت آنتی اکسیدانی کبد دارد-، اثر منفی بر کبد داشته باشد.
کلیدواژه‌ها
عنوان مقاله [English]
The effect of eight weeks of high-intensity interval training with caloric restriction on the expression of SIRT1, ERRα and PDK4 genes in the liver of male Wistar rats: Comparison of high-fat diet and standard diet
نویسندگان [English]
- Zahra Seddighi khovidak 1
- Daruosh Moflehi 2
- Soheil Aminizadeh 3
1 MSc in Exercise Physiology, Department of Physical Education and Sport Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
2 Department of physical education and sport Sciences, Shahid bahonar university of Kerman, Kerman, Iran
3 Department of Physiology and Pharmacology, Afzalipour School of Medicine, and Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
چکیده [English]
Background and Aim: A calorie restriction diet is one way of the ways to reduce calorie intake without malnutrition. The purpose of this study was to investigate the effect of eight weeks of high-intensity interval training with calorie restriction of high-fat or standard diet regimens on the expression of sirtuin 1 (SIRT1), estrogen-related receptor alpha (ERRα) and pyruvate dehydrogenase kinase 4 (PDK4) in the liver of male Wistar rats. Materials and Methods: 48 rats were randomly divided into six groups (n=8): control, high-intensity interval training, high-fat diet with caloric restriction, standard diet with caloric restriction, standard diet with caloric restriction + interval training, and fatty diet with caloric restriction + interval training were divided. High-intensity interval training was performed for 8 weeks and 5 days a week with an intensity of 90 to 100% of the maximum speed in the form of running on a treadmill. Expression of SIRT1, ERRα and PDK4 genes in liver tissue was measured by Real-Time PCR method and one-way ANOVA statistical method was used to compare between groups. Results: Interval training led to a significant increase in ERRα gene expression compared to the control group (p=0.001). Fatty diet with calorie restriction significantly decreased SIRT1 gene expression compared to standard diet with calorie restriction (p=0.002). Also, eight weeks of standard diet with caloric restriction led to a significant increase in PDK4 gene expression compared to the control group (p=0.02). Conclusion: In the condition of calorie restriction, periodic exercise through the up regulation of ERRα gene expression may play a key role in increasing hepatic gluconeogenesis. Interestingly, high-fat diet may have negative effects on the liver even under caloric restriction by reducing the expression of SIRT1, which plays an important role in the antioxidant capacity of the liver.
کلیدواژه‌ها [English]
- High-intensity interval training
- Calorie restriction
- Energy metaboloism
- Gene expression
Aminizadeh, S., Habibi, A., Masoumi-Ardakani, Y., Shahouzehi, B., Marefati, H., & Shakerian, S. (2021). The role of estrogen-related receptor α (ERRα) in metabolic adaptations by endurance training in skeletal muscle of streptozotocin-induced diabetic rats. Sport Sciences for Health, 17(3), 585-596. http://dx.doi.org/10.1007/s11332-020-00714-7
Bakhtiyari, A., Gaeini, A., Chobineh, S., Kordi, M.R., & Hedayati, M. (2018). Effect of 12-week high-intensity interval training on SIRT1, PGC-1α and ERRα protein expression in aged rats. Journal of Applied Health Studies in Sport Physiology, 5(2), 95-102. http://dx.doi.org/10.22049/JASSP.26555.1223.
Billat, L.V. (2001). Interval training for performance: a scientific and empirical practice. Sports Medicine, 31(1), 13-31. http://dx.doi.org/10.2165/00007256-200131010-00002
Boyle, K., Canham, J., Consitt, L., Zheng, D., Koves, T., Gavin, T., … & Muoio, D. (2011). A high-fat diet elicits differential responses in genes coordinating oxidative metabolism in skeletal muscle of lean and obese individuals. The Journal of Clinical Endocrinology & Metabolism, 96(3), 775-781. http://dx.doi.org/10.1210/jc.2010-2253
http://dx.doi.org/10.1210/jc.2010-2253 Chen, Z., Peng, I.C., Cui, X., Li, Y.S., Chien, S., & Shyy, J.Y. (2010). Shear stress, SIRT1, and vascular homeostasis. Proceedings of the National Academy of Sciences, 107(22), 10268-10273. http://dx.doi.org/10.1073/pnas.1003833107
Chen, J., Lin, Y., Li, T., Zhu, H., Huang, F., Yang, C., & Guo, F. (2022). Calorie restriction on normal body weight mice prevents body weight regain on a follow-up high-fat diet by shaping an obesity-resistant-like gut microbiota profile. Food & Function, 13(14), 7684-96. http://dx.doi.org/10.1039/d1fo04358g
Cho, Y., Hazen, B.C., Russell, A.P., & Kralli, A. (2013). Peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-and estrogen-related receptor (ERR)-induced regulator in muscle 1 (Perm1) is a tissue-specific regulator of oxidative capacity in skeletal muscle cells. Journal of Biological Chemistry, 288(35), 25207-25218. http://dx.doi.org/10.1074/jbc.m113.489674
http://dx.doi.org/10.1074/jbc.m113.489674 Civitarese, A.E., Carling, S., Heilbronn, L.K., Hulver, M.H., Ukropcova, B., Deutsch, W.A., … & Ravussin, E. (2007). Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Medicine, 4(3), e76. http://dx.doi.org/10.1371/journal.pmed.0040076
Corbi, G., Conti, V., Scapagnini, G., Filippelli, A., & Ferrara, N. (2012). Role of sirtuins, calorie restriction and physical activity in aging. Frontiers in Bioscience-Elite, 4(2), 768-778. http://dx.doi.org/10.2741/e417
Davis R.A.H., Halbrooks J.E., Watkins E.E., Fisher G., Hunter G.R., & Nagy T.R. (2017). High-intensity interval training and calorie restriction promote remodeling of glucose and lipid metabolism in diet-induced obesity. American Journal of Physiology Endocrinology and Metabolism, 313(2), 243-256. http://dx.doi.org/10.1152/ajpendo.00445.2016
De Mingo, Á., De Gregorio, E., Moles, A., Tarrats, N., Tutusaus, A., Colell, A., … & Marí, M. (2016). Cysteine cathepsins control hepatic NF-κB-dependent inflammation via sirtuin-1 regulation. Cell Death & Disease, 7(11), 2464-2464. http://dx.doi.org/10.1038/cddis.2016.368
http://dx.doi.org/10.1038/cddis.2016.368 Dobrian, A.D., Davies, M.J., Schriver, S.D., Lauterio, T.J., & Prewitt, R.L. (2001). Oxidative stress in a rat model of obesity-induced hypertension. Hypertension, 37(2), 554-560. http://dx.doi.org/10.1161/01.hyp.37.2.554
Fontana, L., Partridge, L., & Longo, V.D. (2010). Extending healthy life span—from yeast to humans. Science, 328(5976), 321-326. http://dx.doi.org/10.1126/science.1172539
Heydari, H., Ghiasi, R., Hamidian, G., Ghaderpour, S., & Keyhanmanesh, R. (2021). Voluntary exercise improves sperm parameters in high fat diet receiving rats through alteration in testicular oxidative stress, mir-34a/SIRT1/p53 and apoptosis. Hormone Molecular Biology and Clinical Investigation, 42(3), 253-263. http://dx.doi.org/10.1515/hmbci-2020-0085
Higashida, K., Kim, S.H., Jung, S.R., Asaka, M., Holloszy, J.O., & Han, D.H. (2013). Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: a reevaluation. PLoS Biology, 11(7), 1001603. http://dx.doi.org/10.1371/journal.pbio.1001603
Høydal, M.A., Wisløff, U., Kemi, O.J., & Ellingsen, Ø. (2007). Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Preventive Cardiology, 14(6), 753-760. http://dx.doi.org/10.1097/hjr.0b013e3281eacef1
Huang, C.C., Wang, T., Tung, Y.T., & Lin, W.T. (2016). Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. International Journal of Medical Sciences, 13(4), 260. http://dx.doi.org/10.7150/ijms.14586
Huss, J.M., Torra, I.P., Staels, B., Giguere, V., & Kelly, D.P. (2004). Estrogen-related receptor α directs peroxisome proliferator-activated receptor α signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Molecular and Cellular Biology, 24(20), 9079-9091. http://dx.doi.org/10.1128/mcb.24.20.9079-9091.2004
Jeoung, N.H., & Harris, R.A. (2008). Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice. American Journal of Physiology-Endocrinology and Metabolism, 295(1), 46-54. http://dx.doi.org/10.1152/ajpendo.00536.2007
Lanvin, O., Bianco, S., Kersual, N., Chalbos, D., & Vanacker, J.M. (2007). Potentiation of ICI182, 780 (Fulvestrant)-induced estrogen receptor-α degradation by the estrogen receptor-related receptor-α inverse agonist XCT790. Journal of Biological Chemistry, 282(39), 28328-28334. http://dx.doi.org/10.1074/jbc.m704295200
Leite A.B., Lima H.N., de Oliveira Flores C., Oliveira C.A., Cunha L.E.C., … & Neves J.L. (2021). High-intensity interval training is more effective than continuous training to reduce inflammation markers in female rats with cisplatin nephrotoxicity. Life Sciences, 266,118880. http://dx.doi.org/10.1016/j.lfs.2020.118880
Lønbro, S., Wiggins, J.M., Wittenborn, T., Elming, P.B., Rice, L., Pampo, C., … & Horsman, M.R. (2019). Reliability of blood lactate as a measure of exercise intensity in different strains of mice during forced treadmill running. Plos One, 14(5), 0215584. http://dx.doi.org/10.1371/journal.pone.0215584
Lozano, I., Van der Werf, R., Bietiger, W., Seyfritz, E., Peronet, C., Pinget, M., … & Sigrist, S. (2016). High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutrition & Metabolism, 13(1), 1-13. http://dx.doi.org/10.1186/s12986-016-0074-1
Ma, L., Dong, W., Wang, R., Li, Y., Xu, B., Zhang, J., … & Wang, Y. (2015). Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice. Brain Research Bulletin, 116, 67-72. http://dx.doi.org/10.1016/j.brainresbull.2015.06.004
Ma, W.Q., Sun, X.J., Zhu, Y., & Liu, N.F. (2020). PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming. Cell Death & Disease, 11(11), 1-23. http://dx.doi.org/10.1038/s41419-020-03162-w
Majer, M., Popov, K.M., Harris, R.A., Bogardus, C., & Prochazka, M. (1998). Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects. Molecular Genetics and Metabolism, 65(2), 181-186. http://dx.doi.org/10.1006/mgme.1998.2748
Mattagajasingh, I., Kim, C.S., Naqvi, A., Yamamori, T., Hoffman, T.A., Jung, S.B., … & Irani, K. (2007). SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proceedings of the National Academy of Sciences, 104(37), 14855-14860. http://dx.doi.org/10.1073/pnas.0704329104
Mattson, M.P. (2005). Energy intake, meal frequency, and health: a neurobiological perspective. Annual Review of Nutrition, 25, 237. http://dx.doi.org/10.1146/annurev.nutr.25.050304.092526
McCay, C.M., Crowell, M.F., & Maynard, L.A. (1935). The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure. The Journal of Nutrition, 10(1), 63-79. http://dx.doi.org/10.1093/jn/10.1.63
Mendes, K.L., de Farias Lelis, D., & Santos, S.H.S. (2017). Nuclear sirtuins and inflammatory signaling pathways. Cytokine & Growth Factor Reviews, 38, 98-105. http://dx.doi.org/10.1016/j.cytogfr.2017.11.001
Mercken, E.M., Crosby, S.D., Lamming, D.W., JeBailey, L., Krzysik‐Walker, S., Villareal, D.T., … & Becker, K. (2013). Calorie restriction in humans inhibits the PI 3 K/AKT pathway and induces a younger transcription profile. Aging Cell, 12(4), 645-651. http://dx.doi.org/10.1111/acel.12088
Nikroo, H., Attarzadeh Hosseini, S.R., Fathi, M., Sardar, M.A., & Khazaei, M. (2020). The effect of aerobic, resistance, and combined training on PPAR-α, SIRT1 gene expression, and insulin resistance in high-fat diet-induced NAFLD male rats. Physiology & Behavior, 227, 113149. http://dx.doi.org/10.1016/j.physbeh.2020.113149
Nordlie, R.C., Foster, J.D., & Lange, A.J. (1999). Regulation of glucose production by the liver. Annual Review of Nutrition, 19, 379. http://dx.doi.org/10.1146/annurev.nutr.19.1.379
Parnow, A., Gharakhanlou, R., Gorginkaraji, Z., Rajabi, S., Eslami, R., Hedayati, M., & Mahdian, R. (2012). Effects of endurance and resistance training on calcitonin gene-related peptide and acetylcholine receptor at slow and fast twitch skeletal muscles and sciatic nerve in male wistar rats. International Journal of Peptides, 2012(2012), 962651. http://dx.doi.org/10.1155/2012/962651
Peters, S.J., Harris, R.A., Wu, P., Pehleman, T.L., Heigenhauser, G.J., & Spriet, L.L. (2001). Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet. American Journal of Physiology-Endocrinology and Metabolism, 281(6), 1151-1158. http://dx.doi.org/10.1152/ajpendo.2001.281.6.e1151
Pfluger, P.T., Herranz, D., Velasco-Miguel, S., Serrano, M., & Tschöp, M.H. (2008). Sirt1 protects against high-fat diet-induced metabolic damage. Proceedings of the National Academy of Sciences, 105(28), 9793-9798. http://dx.doi.org/10.1073/pnas.0802917105
Pilegaard, H., & Neufer, P.D. (2004). Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise. Proceedings of the Nutrition Society, 63(2), 221-226. http://dx.doi.org/10.1079/pns2004345
Pilkis, S.J., & Granner, D. (1992). Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annual Review of Physiology, 54(1), 885-909. http://dx.doi.org/10.1146/annurev.physiol.54.1.885
Rina S., & Tomoaki M. (2020). Effects of using high-intensity interval training and calorie restriction in different orders onmetabolic syndrome: A randomized controlled trial. Nutritin, 75, 110666. http://dx.doi.org/10.1016/j.nut.2019.110666
Rizza, W., Veronese, N., & Fontana, L. (2014). What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Research Reviews, 13, 38-45. http://dx.doi.org/10.1016/j.arr.2013.11.002
Scarpulla, R.C. (2008). Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiological Reviews, 88(2), 611-638. http://dx.doi.org/10.1152/physrev.00025.2007
Schwer, B., & Verdin, E. (2008). Conserved metabolic regulatory functions of sirtuins. Cell Metabolism, 7(2), 104-112. http://dx.doi.org/10.1016/j.cmet.2007.11.006
Teng, C.T., Hsieh, J.H., Zhao, J., Huang, R., Xia, M., Martin, N., … & Witt, K.L. (2017). Development of novel cell lines for high-throughput screening to detect estrogen-related receptor alpha modulators. Slas Dscovery: Advancing Life Sciences R&D, 22(6), 720-731. http://dx.doi.org/10.1177/2472555216689772
Wang, X., Yang, J., Lu, T., Zhan, Z., Wei, W., Lyu, X., … & Xue, X. (2020). The effect of swimming exercise and diet on the hypothalamic inflammation of ApoE-/-mice based on SIRT1-NF-kB-GnRH expression. Aging (Albany NY), 12(11), 11085. http://dx.doi.org/10.18632/aging.103323
Wang, Y. (2014). Molecular links between caloric restriction and Sir2/SIRT1 activation. Diabetes & Metabolism Journal, 38(5), 321-329. http://dx.doi.org/10.4093/dmj.2014.38.5.321
Wende, A.R., Huss, J.M., Schaeffer, P.J., Giguere, V., & Kelly, D.P. (2005). PGC-1α coactivates PDK4 gene expression via the orphan nuclear receptor ERRα: a mechanism for transcriptional control of muscle glucose metabolism. Molecular and Cellular Biology, 25(24), 10684-10694. http://dx.doi.org/10.1128/mcb.25.24.10684-10694.2005
Xia, H., Dufour, C.R., & Giguère, V. (2019). ERRα as a bridge between transcription and function: role in liver metabolism and disease. Frontiers in Endocrinology, 10, 216. http://dx.doi.org/10.3389/fendo.2019.00206
Yoon, J.C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., … & Granner, D.K. (2001). Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature, 413(6852), 131-138. http://dx.doi.org/10.1038/35093050
Zarali, M., Etemad, Z., Azizbeigi, K., & Karimi, P. (2020). Effect of 8 Weeks of High Intensity Interval Training (HIIT) With and Without Calorie Restriction on Gene Expression of Caspase-3 and Caspase-9 Proteins in Male Rats. Journal of Arak University of Medical Sciences, 23(3), 300-313. http://dx.doi.org/10.32598/jams.23.3.5960.1
Zu, Y., Liu, L., Lee, M. Y., Xu, C., Liang, Y., Man, R.Y., … & Wang, Y. (2010). SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circulation Research, 106(8), 1384-1393. http://dx.doi.org/10.1161/circresaha.109.215483
)