Acute exercise increases syndecan-1 and -4 serum concentrations
- 53 Downloads
The effects of acute and long-term exercise on syndecans and the relationship to insulin sensitivity are not fully explored. We aimed to examine the effects of acute and 12 weeks of exercise on (1) serum levels of syndecan-1 and -4, (2) gene expression related to syndecan synthesis and modification in skeletal muscle and adipose tissue, and (3) the relationship to insulin sensitivity. Sedentary men with (n = 13) or without (n = 13) dysglycemia underwent two 45 min acute bicycle tests interspersed by 12 weeks of exercise intervention. Euglycemic hyperinsulinemic clamp and mRNA-sequencing of skeletal muscle and adipose tissue biopsies were performed before and after intervention. Serum syndecan-1 and -4 levels were quantified before, immediately after and 2 h after bicycling. Syndecan-1 and -4 serum concentrations increased in response to acute physical exercise. Baseline syndecan-4 but not syndecan-1 concentrations were higher in dysglycemic compared to normoglycemic men, and correlated to change in insulin sensitivity, but did not change during the 12 weeks exercise intervention. Only syndecan-4 was expressed in skeletal muscle and adipose tissue. Adipose tissue mRNA levels of transcripts affecting syndecan structure and shedding were upregulated in dysglycemia, and muscle mRNA responded to long-term physical activity. The increase in serum syndecan-1 and -4 due to acute exercise suggest increased syndecan shedding and disruption of glycocalyx in response to increased blood flow. The higher syndecan-4 baseline serum levels in dysglycemia, association to insulin sensitivity, and changes in mRNA transcripts may suggest syndecan-4 involvement in muscle and adipose tissue response to exercise.
KeywordsExercise Syndecans Syndecan-shedding Endothelial glycocalyx Dysglycemia Insulin sensitivity
This work was supported by grants from the Institute of Basic Medical Sciences, UiO, Johan Throne-Holst Foundation for Nutrition Research, Freia Medical Research Foundation, the “Functional Genomics” and “Infrastructure” programs of the Research Council of Norway and the Southeastern Regional Health Authorities.
We thank Anne Randi Enget, Ansgar Heck and Birgitte Nellemann for taking the biopsies, and Tor I Gloppen, Torstein Dalen, Håvard Moen, Marius A Dahl, Guro Grøthe, Egil Johansen, Katrine A Krog, Øyvind Skattebo, Daniel S Tangen, Kristoffer K Jensen, Hans K Stadheim, and Eirin Rise for conducting the human strength and endurance intervention (MyoGlu) under supervision of Professor Jørgen Jensen. Sequencing was performed by PhD Gregor Gilfilan at the Norwegian Sequencing Centre (www.sequencing.uio.no) supported by the Research Council of Norway and the South-eastern Regional Health Authorities.
SL analyzed and prepared the data. SL, CAD and TMR interpreted the data and wrote the manuscript. KIB and CAD designed, planned and received grant funding for MyoGlu. All authors reviewed and revised the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the reported research.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Couchman, J.R.: Transmembrane signaling proteoglycans. Annu. Rev. Cell Dev. Biol. 26, 89–114 (2010). https://doi.org/10.1146/annurev-cellbio-100109-104126 CrossRefGoogle Scholar
- 2.Pisconti, A., Bernet, J.D., Olwin, B.B.: Syndecans in skeletal muscle development, regeneration and homeostasis. MLTJ. 2(1), 1–9 (2012)Google Scholar
- 7.Cornelison, D.D., Filla, M.S., Stanley, H.M., Rapraeger, A.C., Olwin, B.B.: Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration. Dev. Biol. 239(1), 79–94 (2001). https://doi.org/10.1006/dbio.2001.0416 CrossRefGoogle Scholar
- 14.Boels, M.G., Avramut, M.C., Koudijs, A., Dane, M.J., Lee, D.H., van der Vlag, J., Koster, A.J., van Zonneveld, A.J., van Faassen, E., Grone, H.J., van den Berg, B.M., Rabelink, T.J.: Atrasentan reduces albuminuria by restoring the glomerular endothelial Glycocalyx barrier in diabetic nephropathy. Diabetes. 65, 2429–2439 (2016). https://doi.org/10.2337/db15-1413 CrossRefGoogle Scholar
- 15.Vuong, T.T., Reine, T.M., Sudworth, A., Jenssen, T., Kolset, S.O.: Syndecan-4 is a major syndecan in primary human endothelial cells in vitro, modulated by inflammatory stimuli and involved in wound healing. J. Histochem. Cytochem. 63(4), 280–292 (2015). https://doi.org/10.1369/0022155415568995
- 17.Svennevig, K., Hoel, T., Thiara, A., Kolset, S., Castelheim, A., Mollnes, T., Brosstad, F., Fosse, E., Svennevig, J.: Syndecan-1 plasma levels during coronary artery bypass surgery with and without cardiopulmonary bypass. Perfusion. 23(3), 165–171 (2008). https://doi.org/10.1177/0267659108098215 CrossRefGoogle Scholar
- 19.Reine, T.M., Kolseth, I.B., Meen, A.J., Lindahl, J.P., Jenssen, T.G., Reinholt, F.P., Zaia, J., Shao, C., Hartmann, A., Kolset, S.O.: Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation. Diabetes Res. Clin. Pract. 107(1), 46–53 (2015). https://doi.org/10.1016/j.diabres.2014.10.006 CrossRefGoogle Scholar
- 20.Solbu, M.D., Kolset, S.O., Jenssen, T.G., Wilsgaard, T., Løchen, M.-L., Mathiesen, E.B., Melsom, T., Eriksen, B.O., Reine, T.M.: Gender Differences in the Association of Syndecan-4 with Myocardial Infarction. The Population-Based Tromsø Study. Atherosclerosis. doi: https://doi.org/10.1016/j.atherosclerosis.2018.08.005, 2018
- 25.Hjorth, M., Norheim, F., Meen, A.J., Pourteymour, S., Lee, S., Holen, T., Jensen, J., Birkeland, K.I., Martinov, V.N., Langleite, T.M., Eckardt, K., Drevon, C.A., Kolset, S.O.: The effect of acute and long-term physical activity on extracellular matrix and serglycin in human skeletal muscle. Physiological Reports. 3(8), (2015). https://doi.org/10.14814/phy2.12473
- 26.Langleite, T.M., Jensen, J., Norheim, F., Gulseth, H.L., Tangen, D.S., Kolnes, K.J., Heck, A., Storas, T., Grothe, G., Dahl, M.A., Kielland, A., Holen, T., Noreng, H.J., Stadheim, H.K., Bjornerud, A., Johansen, E.I., Nellemann, B., Birkeland, K.I., Drevon, C.A.: Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men. Arch. Physiol. Biochem. 122(4), 167–179 (2016). https://doi.org/10.1080/13813455.2016.1202985 CrossRefGoogle Scholar
- 27.Lee, S., Norheim, F., Langleite, T.M., Noreng, H.J., Storas, T.H., Afman, L.A., Frost, G., Bell, J.D., Thomas, E.L., Kolnes, K.J., Tangen, D.S., Stadheim, H.K., Gilfillan, G.D., Gulseth, H.L., Birkeland, K.I., Jensen, J., Drevon, C.A., Holen, T.: Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging. Physiological Reports. 4(21), (2016). https://doi.org/10.14814/phy2.13019
- 28.Li, Y., Lee, S., Langleite, T., Norheim, F., Pourteymour, S., Jensen, J., Stadheim, H.K., Storas, T.H., Davanger, S., Gulseth, H.L., Birkeland, K.I., Drevon, C.A., Holen, T.: Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention. Physiological Reports. 2(11), (2014). https://doi.org/10.14814/phy2.12187
- 29.Norheim, F., Hjorth, M., Langleite, T.M., Lee, S., Holen, T., Bindesboll, C., Stadheim, H.K., Gulseth, H.L., Birkeland, K.I., Kielland, A., Jensen, J., Dalen, K.T., Drevon, C.A.: Regulation of angiopoietin-like protein 4 production during and after exercise. Physiological Reports. 2(8), (2014). https://doi.org/10.14814/phy2.12109
- 30.Majerczak, J., Duda, K., Chlopicki, S., Bartosz, G., Zakrzewska, A., Balcerczyk, A., Smolenski, R.T., Zoladz, J.A.: Endothelial glycocalyx integrity is preserved in young, healthy men during a single bout of strenuous physical exercise. Physiol. Res. 65(2), 281–291 (2016)Google Scholar
- 31.Majerczak, J., Grandys, M., Duda, K., Zakrzewska, A., Balcerczyk, A., Kolodziejski, L., Szymoniak-Chochol, D., Smolenski, R.T., Bartosz, G., Chlopicki, S., Zoladz, J.A.: Moderate-intensity endurance training improves endothelial glycocalyx layer integrity in healthy young men. Exp. Physiol. 102(1), 70–85 (2017). https://doi.org/10.1113/ep085887 CrossRefGoogle Scholar
- 32.Cornelison, D.D., Wilcox-Adelman, S.A., Goetinck, P.F., Rauvala, H., Rapraeger, A.C., Olwin, B.B.: Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration. Genes Dev. 18(18), 2231–2236 (2004). https://doi.org/10.1101/gad.1214204 CrossRefGoogle Scholar
- 36.Lippi, G., Salvagno, G.L., Tarperi, C., Gelati, M., Montagnana, M., Danese, E., Festa, L., Sanchis-Gomar, F., Favaloro, E.J., Schena, F.: Prothrombotic state induced by middle-distance endurance exercise in middle-aged athletes. Semin. Thromb. Hemost. 44, 747–755 (2018). https://doi.org/10.1055/s-0038-1667115 CrossRefGoogle Scholar
- 37.Keller-Pinter, A., Szabo, K., Kocsis, T., Deak, F., Ocsovszki, I., Zvara, A., Puskas, L., Szilak, L., Dux, L.: Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition. FEBS Lett. 592, 3139–3151 (2018). https://doi.org/10.1002/1873-3468.13227 CrossRefGoogle Scholar