The role of miR-17-1-3p in mitochondrial fusion gene expressions and muscle biogenesis with swimming exercise intervention in metabolic syndrome rat model Exercise and miR-17-1-3p

Main Article Content

Muhammed Emre Karaman
Ahmet Tektemur
Muhammed Perihan
Cengiz Arslan
Onur Gursu

Keywords

exercise, metabolic syndrome, miR17-1-3p, mfn1, mfn2, mstn

Abstract

Background and aim: it is known that exercise regulates the expression of mitochondrial fusion and muscle biogenesis involved genes. However, the mechanisms underlying the changes in mitochondrial fusion and muscle metabolism caused by exercise have not been clearly revealed yet. The aim of the study is to elucidate the molecular mechanisms of exercise therapy in metabolic syndrome.


Methods: 21 Sprague-Dawley male rats were used in the styudy and by adding %30 fructose into drinking water Mets were induced after 5 weeks. The rats were randomly divided into 3 groups (Control, MetS, MetS+Exercise) as 7 rats in each cage after feeding for 5 weeks with 30% fructose diet. Swimming exercise were applied to the MetS+Exercise group for six weeks. Once the interventions were finished, the rats were decapitated and dissected to separate the skeletal muscle tissue samples. For the detection of alterations in the expression levels of MFN1, MFN2 and MSTN genes and miR-17-1-3p, the quantitative polymerase chain reaction (qPCR) was performed.


Results: MFN1 and MFN2 expressions upregulated after exercise therapy in intervention group. MSTN and miR-17-1-3p were downregulated after exercise intervention.


Conclusions: it has been shown in the present study, treating MetS with exercise therapy upregulates Mfn1 and Mfn2 gene expressions, which are involved in mitochondrial fusion dynamics, and that MSTN expression, which is increased in MetS, is downregulated by exercise intervention. To the best of our knowledge we demonstrated for the first time that exercise may regulates MSTN, Mfn1 and Mfn2 gene expressions by suppressing miR-17-1-3p.

Abstract 203 | PDF Downloads 113

References

1- Chinnery PF, Hudson G. Mitochondrial genetics. Br Med Bull 2013; 106(1): 135–159.
2- Youle RJ, Van Der Bliek AM. Mitochondrial fission, fusion, and stress. Science 2012; 337(6098): 1062-1065.
3- Arslan M, Atmaca A, Ayvaz G, et al. Metabolic syndrome guide. Turkish Society of Endocrinology and Metabolism 2009.
4- Mahalaxmi G, Ashok S, Arun G, Srinivas G. Albumin binds to uncoupler CCCP to diminish depolarization of mitochondria. Toxicol In Vitro: an international journal published in association with BIBRA 2022; 80: 105325.
5- Tyagi A, Nguyen CU, Chong T, et al. SIRT3 deficiency-induced mitochondrial dysfunction and inflammasome formation in the brain. Sci Rep 2018; 8(1):s 17547.
6- Xue RQ, Yu XJ, Zhao M. et al. Pyridostigmine alleviates cardiac dysfunction via improving mitochondrial cristae shape in a mouse model of metabolic syndrome. Free Radic Biol Med 2019; 134: 119–132.
7- Castillero E, Akashi H, Wang C, et al. Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy. Biochem Biophys Res Commun 2015;457(1): 106-111.
8- Barisione C, Verzola D, Garibaldi S, et al. Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells. Int J Mol Sci 2021; 22(18): 9884.
9- Karaman ME, Arslan C, Gürsu MF, et al. Alterations in Serum Myostatin Levels via Swimming Exercise in High Fructose Mediated Metabolic Syndrome Model. Journal of Pharmaceutical Research International 2021; 33(15): 40-44.
10- He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5(7): 522-531.
11. Aoi W. Frontier impact of microRNAs in skeletal muscle research: a future perspective. Front Physiol 2014: 5(495).
12. Zacharewicz E, Lamon S, Russell AP. MicroRNAs in skeletal muscle and their regulation with exercise, ageing, and disease. Front Physiol 2013; 4(266).
13- Xu T, Liu Q, Yao J, Dai Y, Wang H, Xiao J. Circulating microRNAs in response to exercise. Scand J Med Sci Sports 2015; 25(e): 149–54
14- Christian P, Su Q. MicroRNA regulation of mitochondrial and ER stress signaling pathways: implications for lipoprotein metabolism in metabolic syndrome. Am J Physiol Endocrinol Metab 2014; 307(9): E729-E737.
15- Iqbal J, Al Qarni A, Hawwari A. et al. Metabolic Syndrome, Dyslipidemia and Regulation of Lipoprotein Metabolism. Curr Diabetes Rev 2018; 14(5): 427–433.
16- Noveski P, Popovska-Jankovic K, Kubelka-Sabit K. et al. MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis. Andrology 2016; 4(6): 1020–1027.
17- Yang J, Xu L, Yin X, et al. Excessive Treadmill Training Produces Different Cardiac-related MicroRNA Profiles in the Left and Right Ventricles in Mice. Int J Sports Med 2022; 43(3): 219–229.
18- Schüttler D, Clauss S, Weckbach LT, Brunner S. Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells 2019; 8(10): 1128.
19- Shi J, Bei Y, Kong X, et al. miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury. Theranostics 2017; 7(3): 664–676.
20- Ma Z, Qi J, Meng S, et al. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol 2013;113(10): 2473-2486.
21- Chen J, Huang ZP, Seok HY, et al. mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res 2013;112(12): 1557–1566.
22- Guo G, Liu Y, Ren S, et al. Comprehensive analysis of differentially expressed microRNAs and mRNAs in dorsal root ganglia from streptozotocin-induced diabetic rats. PLoS One 2018; 13(8): e0202696.
23- Li G, Li QS, Li WB, et al. miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy. Neural Regen Res 2016;11(8): 1293.
24- Yang Y, Kai G, Pu XD, et al. Expression profile of microRNAs in fetal lung development of Sprague-Dawley rats. Int J Mol Med2012;29(3): 393-402.
25- Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 1984; 56(4): 831-838.
26- Irazabal MV, Chade AR, Eirin A. Renal mitochondrial injury in the pathogenesis of CKD: mtDNA and mitomiRs. Clin Sci (London, England : 1979) 2022; 136(5): 345–360.
27- Estébanez B, Moreira OC, Almar M, et al. Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects. Eating disorders in athletes: overview of prevalence, risk factors and recommendations for prevention and treatment.Bratland-Sanda S, Sundgot-Borgen J. Eur J Sport Sci 2019; 19(7): 931-940
28- Jeong JH, Koo JH, Yook JS, et al. Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats. Brain Sci 2021; 11(2): 164.
29- Pilar B, Güllich A, Oliveira P, et al. Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome. J Food Sci 2017; 82(12): 3029-3036.
30- Tektemur A, Etem Önalan E, Kaya Tektemur N. Carbamazepine-induced sperm disorders can be associated with the altered expressions of testicular KCNJ11/miR-let-7a and spermatozoal CFTR/miR-27a. Andrologia 2021; 53(2): e13954.
31- Mitchell T, Darley-Usmar V. Metabolic syndrome and mitochondrial dysfunction: insights from pre-clinical studies with a mitochondrially targeted antioxidant. Free Radic Biol Med 2012; 52(5): 838.
32- Durak A, Olgar Y, Degirmenci. et al. A SGLT2 inhibitor dapagliflozin suppresses prolonged ventricular-repolarization through augmentation of mitochondrial function in insulin-resistant metabolic syndrome rats. Cardiovasc Diabetol 2018; 17(1): 144.
33- Marzetti E, Calvani R, Cesari M, et al. vMitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials. Int J Biochem Cell Biol 2013; 45(10): 2288- 2301.
34- Ziaaldini MM, Hosseini SA, Fathi M. Mitochondrial adaptations in aged skeletal muscle: effect of exercise training. Physiological research 2017; 66(1).
35- Kim JH, Kim JH, Jang JP, et al. Identification of Molecules from Coffee Silverskin That Suppresses Myostatin Activity and Improves Muscle Mass and Strength in Mice. Molecules (Basel, Switzerland) 2021; 26(9): 2676.
36- Carvalho LP, Basso-Vanelli RP, Di Thommazo-Luporini L, et al. Myostatin and adipokines: The role of the metabolically unhealthy obese phenotype in muscle function and aerobic capacity in young adults. Cytokine 2018; 107: 118–124.
37- Dong J, Dong Y, Chen F, et al. Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated cross talk between muscle and adipose tissues. The age of obesity. Howard AN, Bray GA. Int J Obes 2016; 40(3): 434-442.
38- Hittel DS, Axelson M, Sarna N, et al. Myostatin decreases with aerobic exercise and associates with insulin resistance. Med Sci Sports Exerc 2010; 42(11): 2023.
39- Tang L, Zhao T, Kang Y, et al. MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats. J Physiol Biochem 2022; 78(1): 61–72.
40- Hulmi JJ, Kovanen V, Selänne H, et al. Acute and long-term effects of resistance exercise with or without protein ingestion on muscle hypertrophy and gene expression. Amino acids 2009; 37(2): 297-308.
41- Kim JS, Cross JM, Bamman MM. Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women. Am J Physiol Endocrinol Metab 2005; 288(6): E1110-E1119.
42- Liu J, Yu P, Lv W, et al. The 24-Form Tai Chi Improves Anxiety and Depression and Upregulates miR-17-92 in Coronary Heart Disease Patients After Percutaneous Coronary Intervention. Front Physiol 2020; 11:149.
42- Ramzan F, D'Souza RF, Durainayagam BR, et al. Circulatory miRNA biomarkers of metabolic syndrome. Acta Diabetol 2020; 57(2): 203–214.
43- Kannu P, Campos-Xavier AB, Hull D, et al. Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5. Eur J Med Genet 2013; 56(8): 452–457.
43- Mohan S, Wergedal JE, Das S, et al. Conditional disruption of miR17-92 cluster in collagen type I-producing osteoblasts results in reduced periosteal bone formation and bone anabolic response to exercise. Physiol Genomics 2015; 47(2): 33–43.
44- Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res 2020; 48(D1): D127-D131.