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Int J Sports Med 2016; 37(07): 584-588
DOI: 10.1055/s-0035-1569345
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

Αcute Exercise Alters the Levels of Human Saliva miRNAs Involved in Lipid Metabolism

A. Konstantinidou
1   Dietetics and Nutritional Science, Harokopio University, Athens, Greece
,
V. Mougios
2   School of Physical Education and Sport Science, Aristotle University, Thessaloniki, Greece
,
L. S. Sidossis
3   Department of Internal Medicine, University of Texas Medical Branch, Galveston, United States
› Author Affiliations
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Publication History



accepted after revision 30 November 2015

Publication Date:
26 April 2016 (online)

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Abstract

The response of micro-ribonucleic acid (miRNA) expression to exercise has not been studied in saliva, although saliva combines non-invasive collection with the largest number of miRNA species among biological fluids and tissues. Thus, the purpose of this study was to investigate the effect of acute exercise on the expression of 8 human saliva miRNAs involved in lipid metabolism. 19 healthy, physically active men (VO2max, 40.9±1.6 mL·kg–1·min–1, mean±se) performed a 50-min interval exercise program on stationary bicycle (spinning). Saliva samples were collected before and after exercise for miRNA expression analysis by real-time polymerase chain reaction. Statistically significant (p<0.05) changes after exercise were found in 2 of the 8 miRNAs, namely, hsa-miR-33a (fold change, 7.66±2.94; p=0.012), which regulates cholesterol homeostasis and fatty acid metabolism in the liver, and hsa-miR-378a (fold change 0.79±0.11, p=0.048), which regulates energy homeostasis and affects lipogenesis and adipogenesis. These alterations may contribute to our understanding of physiological responses to exercise and the therapeutic potential of exercise against cardiovascular disease, obesity, and the metabolic syndrome. Moreover, our findings open the possibility of noninvasively studying miRNAs that regulate the function of specific organs.

Key words

hsa-miR-33a - hsa-miR-378a - real-time polymerase chain reaction - spinning exercise
 

  • References

  • 1 Ambros V. The functions of animal microRNAs. Nature 2004; 431: 350-355
    CrossrefPubMedGoogle Scholar
  • 2 Aoi W, Ichikawa H, Mune K, Tanimura Y, Mizushima K, Naito Y, Yoshikawa T. Muscle-enriched microRNA miR-486 decreases in circulation in response to exercise in young men. Front Physiol 2013; 4 DOI: 10.3389/fphys.2013.00080.
    PubMedGoogle Scholar
  • 3 Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, Wang TJ, Chan SY. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol 2011; 589: 3983-3994
    CrossrefPubMedGoogle Scholar
  • 4 Bahn JH, Zhang Q, Li F, Chan TM, Lin X, Kim Y, Wong DT, Xiao X. The landscape of microRNA, piwi-interacting RNA, and circular RNA in human saliva. Clin Chem 2015; 61: 221-230
    CrossrefPubMedGoogle Scholar
  • 5 Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136: 215-233
    CrossrefPubMedGoogle Scholar
  • 6 Braoudaki M, Lambrou GI, Giannikou K, Milionis V, Stefanaki K, Birks DK, Prodromou N, Kolialexi A, Kattamis A, Spiliopoulou CA, Tzortzatou-Stathopoulou F, Kanavakis E. Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms. J. Hematol Oncol 2014; 7: 96 DOI: 10.1186/s13045-014-0096-y.
    CrossrefPubMedGoogle Scholar
  • 7 Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378 *. Proc Natl Acad Sci USA 2012; 109: 15330-15335
    CrossrefPubMedGoogle Scholar
  • 8 Chen WJ, Yin K, Zhao GJ, Fu YC, Tang CK. The magic and mystery of microRNA-27 in atherosclerosis. Atherosclerosis 2012; 222: 314-323
    CrossrefPubMedGoogle Scholar
  • 9 Chen WJ, Zhang M, Zhao GJ, Fu Y, Zhang DW, Zhu HB, Tang CK. MicroRNA-33 in atherosclerosis etiology and pathophysiology. Atherosclerosis 2013; 227: 201-208
    CrossrefPubMedGoogle Scholar
  • 10 Chicharro JL, Lucía A, Pérez M, Vaquero AF, Ureña R. Saliva composition and exercise. Sports Med 1998; 26: 17-27
    CrossrefPubMedGoogle Scholar
  • 11 Cordente AG, López-Viñas E, Vázquez MI, Swiegers JH, Pretorius IS, Gómez-Puertas P, Hegardt FG, Asins G, Serra D. Redesign of carnitine acetyltransferase specificity by protein engineering. J Biol Chem 2004; 279: 33899-33908
    CrossrefPubMedGoogle Scholar
  • 12 Davidsen PK, Gallagher IJ, Hartman JW, Tarnopolsky MA, Dela F, Helge JW, Timmons JA, Phillips SM. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J Appl Physiol 2011; 110: 309-317
    CrossrefPubMedGoogle Scholar
  • 13 Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 2004; 279: 52361-52365
    CrossrefPubMedGoogle Scholar
  • 14 Fernández-Hernando C, Suárez Y, Rayner KJ, Moore KJ. MicroRNAs in lipid metabolism. Curr Opin Lipidol 2011; 22: 86-92
    CrossrefPubMedGoogle Scholar
  • 15 Flowers E, Froelicher ES, Aouizerat BE. MicroRNA regulation of lipid metabolism. Metabolism 2013; 62: 12-20
    CrossrefPubMedGoogle Scholar
  • 16 Gatti R, De Palo EF. An update: salivary hormones and physical exercise. Scand J Med Sci Sports 2011; 21: 157-169
    CrossrefPubMedGoogle Scholar
  • 17 Gerin I, Bommer GT, McCoin CS, Sousa KM, Krishnan V, MacDougald OA. Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis. Am J Physiol
    PubMedGoogle Scholar
  • 18 Gim JA, Ayarpadikannan S, Eo J, Kwon YJ, Choi Y, Lee HK, Park KD, Yang YM, Cho BW, Kim HS. Transcriptional expression changes of glucose metabolism genes after exercise in thoroughbred horses. Gene 2014; 547: 152-158
    CrossrefPubMedGoogle Scholar
  • 19 Harriss DJ, Atkinson G. Ethical standards in sports and exercise science research. 2016 update Int J Sports Med 2015; 36: 1121-1124
    Google Scholar
  • 20 Hatse S, Brouwers B, Dalmasso B, Laenen A, Kenis C, Schoffski P, Wildiers H. Circulating microRNAs as easy-to-measure aging biomarkers in older breast cancer patients: correlation with chronological age but not with fitness/frailty status. PLoS ONE 9 e110644
    PubMedGoogle Scholar
  • 21 Iliopoulos D, Drosatos K, Hiyama Y, Goldberg IJ, Zannis VI. MicroRNA-370 controls the expression of microRNA-122 and Cpt1α and affects lipid metabolism. J Lipid Res 2010; 51: 1513-1523
    CrossrefPubMedGoogle Scholar
  • 22 Lässer C, Alikhani VS, Ekström K, Eldh M, Paredes PT, Bossios A, Sjöstrand 1 M, Gabrielsson S, Lötvall J, Valadi H. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med 2011; 9: 9
    CrossrefPubMedGoogle Scholar
  • 23 Li H, Zhang Z, Zhou X, Wang Z, Wang G, Han Z. Effects of microRNA-143 in the differentiation and proliferation of bovine intramuscular preadipocytes. Mol Biol Rep 2011; 38: 4273-4280
    CrossrefPubMedGoogle Scholar
  • 24 Mougios V. Exercise Biochemistry. Champaign: Human Kinetics; 2006: 208
    Google Scholar
  • 25 Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H. The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun 2009; 385: 492-496
    CrossrefPubMedGoogle Scholar
  • 26 Nielsen S, Scheele C, Yfanti C, Akerström T, Nielsen AR, Pedersen BK, Laye MJ. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol 2010; 588: 4029-4037
    CrossrefPubMedGoogle Scholar
  • 27 Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 2009; 15: 5473-5477
    CrossrefPubMedGoogle Scholar
  • 28 Radom-Aizik S, Zaldivar F, Haddad F, Cooper DM. Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults. J Appl Physiol 2013; 114: 628-636
    CrossrefPubMedGoogle Scholar
  • 29 Radom-Aizik S, Zaldivar F, Haddar F, Cooper DM. Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease. Brain Behav Immun 2014; 39: 121-129
    CrossrefPubMedGoogle Scholar
  • 30 Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, Ray TD, Sheedy FJ, Goedeke L, Liu X, Khatsenko OG, Kaimal V, Lees CJ, Fernandez-Hernando 1 C, Fisher EA, Temel RE, Moore KJ. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 2011; 478: 404-407
    CrossrefPubMedGoogle Scholar
  • 31 Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res 2004; 14: 1902-1910
    CrossrefPubMedGoogle Scholar
  • 32 Sacco J, Adeli K. MicroRNAs: emerging roles in lipid and lipoprotein metabolism. Curr Opin Lipidol 2012; 23: 220-225
    CrossrefPubMedGoogle Scholar
  • 33 Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654-659
    CrossrefPubMedGoogle Scholar
  • 34 Vickers KC, Shoucri BM, Levin MG, Wu H, Pearson DS, Osei-Hwedieh D, Collins FS, Remaley AT, Sethupathy P. MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. Hepatology 2013; 57: 533-542
    CrossrefPubMedGoogle Scholar
  • 35 Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56: 1733-1741
    CrossrefPubMedGoogle Scholar
  • 36 Wiklund ED, Gao S, Hulf T, Sibbritt T, Nair S, Costea DE, Villadsen SB, Bakholdt V, Bramsen JB, Sørensen JA, Krogdahl A, Clark SJ, Kjems J. MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma. PLoS ONE 2011; 6 e27840
    PubMedGoogle Scholar
  • 37 Xie Z, Chen G, Zhang X, Li D, Huang J, Yang C, Zhang P, Qin Y, Duan Y, Gong B, Li Z. Salivary MicroRNAs as promising biomarkers for detection of esophageal cancer. PLoS ONE 2013; 8 e57502
    PubMedGoogle Scholar
  • 38 Yang K, He YS, Wang XQ, Lu L, Chen QJ, Liu J, Sun Z, Shen WF. MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4. FEBS Lett 2011; 585: 854-860
    CrossrefPubMedGoogle Scholar