تاثیر تمرین هوازی تداومی همراه با مصرف بهار نارنج بر بیان ژن‌های HM و MOTS-C میتوکندری بافت کبد موش های بزرگ سالمند

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه تربیت بدنی وعلوم ورزشی، واحد قائمشهر، دانشگاه آزاد اسلامی، قائمشهر، ایران

10.22070/daneshmed.2024.19122.1493

چکیده

مقدمه و هدف: روند افزایش سن با اختلال در میتوکندری و کبد همراه است. هدف از این مطالعه تبیین تأثیر تمرین هوازی تداومی همراه با مصرف بهار نارنج بر بیان ژن‌های HM و MOTS-C میتوکندری بافت کبد رت‌های سالمند بود.
مواد و روش ها: برای انجام تحقیق آزمایشی حاضر 32 سر موش صحرایی ماده سالمند بالای 14 ماه سن و میانگین وزن  270 الی 320 گرم در 4 گروه 8 سری شامل 1- کنترل (CN)، 2- مصرف عصاره بهار نارنج (CA)، 3- تمرین (T)، 4- تمرین و مصرف عصاره بهار نارنج (T+CA) قرار گرفتند. در مدت هشت هفته گروه‌های 3 و 4 به میزان سه جلسه در هفته با شدت 65 تا 75 درصد حداکثر سرعت دویدن روی نوارگردان دویدند؛ همچنین گروه‌های 2 و 4 روزانه mg/kg 300 عصاره CA به صورت صفاقی دریافت نمودند. 48 ساعت پس از پروتکل تحقیق سطوح بیان ژنی در بافت کبد به روش real- time PCR اندازه‌گیری شد.
نتایج: بیان ژن‌های HM و MOTS-C در گروه‌های CA (032/0p= و 042/0p=)، T (039/0p= و 048/0p=) و T+CA (0001/0p= و 001/0p=) نسبت به گروه CN افزایش معنی‌داری داشت.
نتیجه‌گیری: هشت هفته تمرین و مکمل به تنهایی منجر به بهبود پپتیدهای مشتق از میتوکندری در بافت کبد موش‌های صحرایی سالمند شد. همچنین اثر همزمان تمرین  و CA بر HM بیشتر از اثر هر کدام به تنهایی بود.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The Effect of continuous aerobic exercise with Citrus aurantium L. on the expression of HM and MOTS-C genes in the mitochondria of the liver tissue of aged rats

نویسندگان [English]

  • Saba Ahmadi
  • Saqqa Farajtabar Behrestaq
  • Masoumeh Habibian
  • Babisan Askari
  • Amir Taghipour
Department of Physical Education and Sport Sciences, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
چکیده [English]

Background and Objective: Aging process is associated with disruption in mitochondria and liver. The aim of this study was to was to evaluate the effect of continuous aerobic exercise with citrus aurantium L. on the expression of HM and MOTS-C genes in the mitochondria of the liver tissue of elderly rats.
Materials and Methods: To conduct the present experimental research, 32 elderly female rats over 14 months of age and average weight of 270 to 320 grams were divided into 4 groups of 8 including 1- Control (CN), 2- Consumption of citrus aurantium L. (CA), 3- Training (T), 4- Training and consumption of citrus aurantium L. (T+CA). During eight weeks, groups 3 and 4 ran three sessions a week with an intensity of 65-75% of the maximum running speed on the treadmill. Also, groups 2 and 4 received 300 mg/kg of CA extract intraperitoneally. 48 hours after the research protocol, gene expression levels in liver tissue were measured by real-time PCR method.
Results: Expression of HM and MOTS-C genes in CA (p=0.032 and p=0.042), T (p=0.039 and p=0.048) and T+CA (p=0.0001 and p=0.001) groups compared to CN group had a significant increase.
Conclusion: Eight weeks of T and CA alone improved the expression of genes involved in Liver cellular senescence markers of elderly rats. Also, the simultaneous effect of exercise and CA on HM was greater than the effect of each one alone.

کلیدواژه‌ها [English]

  • Training
  • Citrus aurantium
  • Mitochondria
  • HM
  • MOTS-C
  1. Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications 2020;11(1):102.
  2. Kim S-J, Miller B, Kumagai H, Silverstein AR, Flores M, et al. Mitochondrial-derived peptides in aging and age-related diseases. Geroscience. 2021;43:1113-21.
  3. Siasos G, Tsigkou V, Kosmopoulos M, Theodosiadis D, Simantiris S, Tagkou NM, et al. Mitochondria and cardiovascular diseases—from pathophysiology to treatment. Annals of Translational Medicine 2018;6:(12).
  4. Lee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends in Endocrinology & Metabolism 2013;24(5):222-228.
  5. Kim KH, Son JM, Benayoun BA, Lee C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metabolism 2018;28(3):516-24. e7.
  6. Qin Q, Delrio S, Wan J, Widmer RJ, Cohen P, Lerman LO, et al. Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. International Journal of Cardiology 2018;254:23-27.
  7. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a tool to target aging. Cell metabolism 2016;23(6):1060-1065.
  8. Yen K, Mehta HH, Kim S-J, Lue Y, Hoang J, Guerrero N, et al. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). 2020;12(12):11185.
  9. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015;21(3):443-454.
  10. Nashine S, Kenney MC. Effects of mitochondrial-derived peptides (MDPs) on mitochondrial and cellular health in AMD. Cells 2020;9(5):1102.
  11. Hoang PT, Park P, Cobb LJ, Paharkova-Vatchkova V, Hakimi M, Cohen P, et al. The neurosurvival factor Humanin inhibits β-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice. Metabolism 2010;59(3):343-349.
  12. Cobb LJ, Lee C, Xiao J, Yen K, Wong RG, Nakamura HK, et al. Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY) 2016;8(4):796.
  13. Reynolds JC, Lai RW, Woodhead JS, Joly JH, Mitchell CJ, Cameron-Smith D, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications 2021;12(1):1-11.
  14. Gong Z, Su K, Cui L, Tas E, Zhang T, Dong HH, et al. Central effects of humanin on hepatic triglyceride secretion. American Journal of Physiology-Endocrinology and Metabolism 2015;309(3):E283-E92.
  15. Gidlund EK, von Walden F, Venojärvi M, Risérus U, Heinonen OJ, Norrbom J, et al. Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism. Physiological Reports 2016;4(23):e13063.
  16. Suntar I, Khan H, Patel S, Celano R, Rastrelli L. An overview on Citrus aurantium L.: its functions as food ingredient and therapeutic agent. Oxidative Medicine and Cellular Longevity 2018. doi: 10.1155/2018/7864269
  17. Hafidh RR, Hussein SZ, MalAllah MQ, Abdulamir AS, Abu Bakar F. A high-throughput quantitative expression analysis of cancer-related genes in human HepG2 cells in response to limonene, a potential anticancer agent. Current Cancer Drug Targets 2018;18(8):807-815.
  18. 18-Zhao H-Y, Yang L, Wei J, Huang M, Jiang J-G. Bioactivity evaluations of ingredients extracted from the flowers of Citrus aurantium L. var. amara Engl. Food Chemistry 2012;135(4):2175-2181.
  19. Yazdanparast Chaharmahali B, Azarbayjani MA, Peeri M, Farzanegi Arkhazloo P. The Effect of Moderate and High Intensity Interval Trainings on Cardiac Apoptosis in the Old Female Rats. Report of Health Care 2018;4(1):26-35.
  20. 20-He W, Li Y, Liu M, Yu H, Chen Q, Chen Y, et al. Citrus aurantium L. and its flavonoids regulate TNBS-induced inflammatory bowel disease through anti-inflammation and suppressing isolated jejunum contraction. International Journal of Molecular Sciences 2018;19(10):3057.
  21. Dieli-Conwright CM, Sami N, Norris MK, Wan J, Kumagai H, Kim S-J, et al. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Scientific Reports 2021;11(1):1-7.
  22. Guo Q, Chang B, Yu Q-l, Xu S-t, Yi X-j, Cao S-c. Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1–SIRT1–PGC-1α. Diabetologia 2020;63(12):2675-2688.
  23. Yang B, Yu Q, Chang B, Guo Q, Xu S, Yi X, et al. MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2021;1867(6):166126.
  24. Woodhead JS, D’Souza RF, Hedges CP, Wan J, Berridge MV, Cameron-Smith D, et al. High-intensity interval exercise increases humanin, a mitochondrial encoded peptide, in the plasma and muscle of men. Journal of Applied Physiology. 2020;128(5):1346-1354.
  25. Woodhead JS, Merry TL. Mitochondrial-derived peptides and exercise. Biochimica et Biophysica Acta (BBA)-General Subjects. 2021;1865(12):130011.
  26. Crimmins EM. Lifespan and healthspan: past, present, and promise. The Gerontologist 2015;55(6):901-911.
  27. Fan W, Evans RM. Exercise mimetics: impact on health and performance. Cell metabolism. 2017;25(2):242-7.
  28. Guan Y, Drake JC, Yan Z. Exercise-induced mitophagy in skeletal muscle and heart. Exercise and Sport Sciences Reviews 2019;47(3):151.
  29. von Walden F, Fernandez-Gonzalo R, Norrbom J, Emanuelsson EB, Figueiredo VC, Gidlund E-K, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. Journal of Applied Physiology 2021;131(3):1035-1042.
  30. Ramanjaneya M, Jerobin J, Bettahi I, Bensila M, Aye M, Siveen KS, et al. Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects. Clinical Endocrinology 2019;91(2):278-287.
  31. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 2006;127(6):1109-1122.
  32. Bare G-HZRJ. O. Lerin C. Kim SH Mostoslavsky R. Alt FW Wu Z. Puigserver P. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO Journal 2007;26:1913-1923.