Skip to main content

Advertisement

Log in

Daily regulation of serum and urinary hepcidin is not influenced by submaximal cycling exercise in humans with normal iron metabolism

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Hepcidin and hemojuvelin (HJV) are two critical regulators of iron metabolism as indicated by the development of major iron overload associated to mutations in hepcidin and HJV genes. Hepcidin and HJV are highly expressed in liver and muscles, respectively. Intensive muscular exercise has been reported to modify serum iron parameters and to increase hepcidinuria. The present study aimed at evaluating the potential impact of low intensity muscle exercise on iron metabolism and on hepcidin, its key regulator. Fourteen normal volunteers underwent submaximal cycling-based exercise in a crossover design and various iron parameters, including serum and urinary hepcidin, were serially studied. The results demonstrated that submaximal ergocycle endurance exercise did not modulate hepcidin. This study also indicated that hepcidinuria did not show any daily variation whereas serum hepcidin did. The findings, by demonstrating that hepcidin concentrations are not influenced by submaximal cycling exercise, may have implications for hepcidin sampling in medical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aguilar Martinez P, Schved JF, Brissot P (2005) The evaluation of hyperferritinemia: an updated strategy based on advances in detecting genetic abnormalities. Am J Gastroenterol 100:1185–1194. doi:10.1111/j.1572-0241.2005.40998.x

    Article  PubMed  CAS  Google Scholar 

  • Ahmadi S, Sinclair PJ, Davis GM (2008) Muscle oxygenation after downhill walking-induced muscle damage. Clin Physiol Funct Imaging 28:55–63

    PubMed  Google Scholar 

  • Andrews NC (1999) Disorders of iron metabolism. N Engl J Med 341:1986–1995. doi:10.1056/NEJM199912233412607

    Article  PubMed  CAS  Google Scholar 

  • Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, Campagna JA, Chung RT, Schneyer AL, Woolf CJ, Andrews NC, Lin HY (2006) Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38:531–539. doi:10.1038/ng1777

    Article  PubMed  CAS  Google Scholar 

  • Balaban EP, Cox JV, Snell P, Vaughan RH, Frenkel EP (1989) The frequency of anemia and iron deficiency in the runner. Med Sci Sports Exerc 21:643–648. doi:10.1249/00005768-198912000-00003

    PubMed  CAS  Google Scholar 

  • Besson C, Rochcongar P, Beauverger Y, Dassonville J, Aubree M, Catheline M (1981) Study of the valuations of serum muscular enzymes and myoglobin after maximal exercise test and during the next 24 hours. Eur J Appl Physiol Occup Physiol 47:47–56. doi:10.1007/BF00422482

    Article  PubMed  CAS  Google Scholar 

  • Brissot P, Troadec MB, Bardou-Jacquet E, Lan CL, Jouanolle AM, Deugnier Y, Loreal O (2008) Current approach to hemochromatosis. Blood Rev 22:195–210. doi:10.1016/j.blre.2008.03.001

    Article  PubMed  Google Scholar 

  • Di Santolo M, Stel G, Banfi G, Gonano F, Cauci S (2008) Anemia and iron status in young fertile non-professional female athletes. Eur J Appl Physiol 102:703–709. doi:10.1007/s00421-007-0647-9

    Article  PubMed  CAS  Google Scholar 

  • Ehn L, Carlmark B, Hoglund S (1980) Iron status in athletes involved in intense physical activity. Med Sci Sports Exerc 12:61–64. doi:10.1249/00005768-198021000-00012

    PubMed  CAS  Google Scholar 

  • Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M (2008) Immunoassay for human serum hepcidin. Blood 112:4292–4297. doi:10.1182/blood-2008-02-139915

    Article  PubMed  CAS  Google Scholar 

  • Goebel MU, Mills PJ, Irwin MR, Ziegler MG (2000) Interleukin-6 and tumor necrosis factor-alpha production after acute psychological stress, exercise, and infused isoproterenol: differential effects and pathways. Psychosom Med 62:591–598

    PubMed  CAS  Google Scholar 

  • Gropper SS, Blessing D, Dunham K, Barksdale JM (2006) Iron status of female collegiate athletes involved in different sports. Biol Trace Elem Res 109:1–14. doi:10.1385/BTER:109:1:001

    Article  PubMed  CAS  Google Scholar 

  • Guillygomarc’h A, Christian J, Romain M, Vincent Q, Veronique D, Deugnier Y (2003) Circadian variations of transferrin saturation levels in iron-overloaded patients: implications for the screening of C282Y-linked haemochromatosis. Br J Haematol 120:359–363. doi:10.1046/j.1365-2141.2003.04070.x

    Article  PubMed  Google Scholar 

  • Hood DA, Kelton R, Nishio ML (1992) Mitochondrial adaptations to chronic muscle use: effect of iron deficiency. Comp Biochem Physiol Comp Physiol 101:597–605. doi:10.1016/0300-9629(92)90514-Q

    Article  PubMed  CAS  Google Scholar 

  • Huang FW, Pinkus JL, Pinkus GS, Fleming MD, Andrews NC (2005) A mouse model of juvenile hemochromatosis. J Clin Invest 115:2187–2191. doi:10.1172/JCI25049

    Article  PubMed  CAS  Google Scholar 

  • Kemna EH, Tjalsma H, Podust VN, Swinkels DW (2007) Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 53:620–628. doi:10.1373/clinchem.2006.079186

    Article  PubMed  CAS  Google Scholar 

  • Kivela R, Kyrolainen H, Selanne H, Komi PV, Kainulainen H, Vihko V (2007) A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle. J Appl Physiol 103:1395–1401. doi:10.1152/japplphysiol.00531.2007

    Article  PubMed  CAS  Google Scholar 

  • Lin L, Goldberg YP, Ganz T (2005) Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood 106:2884–2889. doi:10.1182/blood-2005-05-1845

    Article  PubMed  CAS  Google Scholar 

  • Magnusson B, Hallberg L, Rossander L, Swolin B (1984) Iron metabolism and “sports anemia”. II. A hematological comparison of elite runners and control subjects. Acta Med Scand 216:157–164

    PubMed  CAS  Google Scholar 

  • Monnier PP, Sierra A, Macchi P, Deitinghoff L, Andersen JS, Mann M, Flad M, Hornberger MR, Stahl B, Bonhoeffer F, Mueller BK (2002) RGM is a repulsive guidance molecule for retinal axons. Nature 419:392–395. doi:10.1038/nature01041

    Article  PubMed  CAS  Google Scholar 

  • Nachtigall D, Nielsen P, Fischer R, Engelhardt R, Gabbe EE (1996) Iron deficiency in distance runners. A reinvestigation using Fe-labelling and non-invasive liver iron quantification. Int J Sports Med 17:473–479. doi:10.1055/s-2007-972881

    Article  PubMed  CAS  Google Scholar 

  • Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T (2003) Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101:2461–2463. doi:10.1182/blood-2002-10-3235

    Article  PubMed  CAS  Google Scholar 

  • Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276

    PubMed  CAS  Google Scholar 

  • Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780–8785. doi:10.1073/pnas.151179498

    Article  PubMed  CAS  Google Scholar 

  • Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S (2002) Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 99:4596–4601. doi:10.1073/pnas.072632499

    Article  PubMed  CAS  Google Scholar 

  • Niederkofler V, Salie R, Sigrist M, Arber S (2004) Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J Neurosci 24:808–818. doi:10.1523/JNEUROSCI.4610-03.2004

    Article  PubMed  CAS  Google Scholar 

  • Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP (2004) Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36:77–82. doi:10.1038/ng1274

    Article  PubMed  CAS  Google Scholar 

  • Pedersen BK, Akerstrom TC, Nielsen AR, Fischer CP (2007) Role of myokines in exercise and metabolism. J Appl Physiol 103:1093–1098. doi:10.1152/japplphysiol.00080.2007

    Article  PubMed  CAS  Google Scholar 

  • Peeling P, Dawson B, Goodman C, Landers G, Trinder D (2008) Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 103:381–391. doi:10.1007/s00421-008-0726-6

    Article  PubMed  CAS  Google Scholar 

  • Peeling P, Dawson B, Goodman C, Landers G, Wiegerinck ET, Swinkels DW, Trinder D (2009) Cumulative effects of consecutive running sessions on hemolysis, inflammation and hepcidin activity. Eur J Appl Physiol 31 (Epub ahead of print)

  • Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811–7819. doi:10.1074/jbc.M008923200

    Article  PubMed  CAS  Google Scholar 

  • Robach P, Cairo G, Gelfi C, Bernuzzi F, Pilegaard H, Vigano A, Santambrogio P, Cerretelli P, Calbet JA, Moutereau S, Lundby C (2007) Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle. Blood 109:4724–4731. doi:10.1182/blood-2006-08-040006

    Article  PubMed  CAS  Google Scholar 

  • Rocker L, Hinz K, Holland K, Gunga HC, Vogelgesang J, Kiesewetter H (2002) Influence of endurance exercise (triathlon) on circulating transferrin receptors and other indicators of iron status in female athletes. Clin Lab (Zaragoza) 48:307–312

    CAS  Google Scholar 

  • Roecker L, Meier-Buttermilch R, Brechtel L, Nemeth E, Ganz T (2005) Iron-regulatory protein hepcidin is increased in female athletes after a marathon. Eur J Appl Physiol 95:569–571. doi:10.1007/s00421-005-0055-y

    Article  PubMed  CAS  Google Scholar 

  • Samad TA, Srinivasan A, Karchewski LA, Jeong SJ, Campagna JA, Ji RR, Fabrizio DA, Zhang Y, Lin HY, Bell E, Woolf CJ (2004) DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci 24:2027–2036. doi:10.1523/JNEUROSCI.4115-03.2004

    Article  PubMed  CAS  Google Scholar 

  • Schumacher YO, Schmid A, Konig D, Berg A (2002) Effects of exercise on soluble transferrin receptor and other variables of the iron status. Br J Sports Med 36:195–199. doi:10.1136/bjsm.36.3.195

    Article  PubMed  Google Scholar 

  • Wiltink WF, Kruithof J, Mol C, Bos MG, van Eijk HG (1973) Diurnal and nocturnal variations of the serum iron in normal subjects. Clin Chim Acta 49:99–104. doi:10.1016/0009-8981(73)90348-3

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Chen J, Wang W, Wang L, Ma L, Shen H, Li M (2008) Psychological stress induces hypoferremia through the IL-6-hepcidin axis in rats. Biochem Biophys Res Commun 373:90–93. doi:10.1016/j.bbrc.2008.05.166

    Article  PubMed  CAS  Google Scholar 

  • Zoller H, Vogel W (2004) Iron supplementation in athletes–first do no harm. Nutrition 20:615–619. doi:10.1016/j.nut.2004.04.006

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by COREC (Comité de Recherche Clinique) 2005 (University Hospital, Rennes), Association Fer et Foie, and by European Contract EuroIron1 (STREP No. 037296).

Conflict of interest statement

Mark Westerman is Co-founder and President of Intrinsic Life Sciences. Tomas Ganz and Elizabeta Nemeth are Co-founders and Members of the Advisory Board for Intrinsic Life Sciences. Olbina Gordana is a Senior Scientist from Intrinsic Life Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marie-Bérengère Troadec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Troadec, MB., Lainé, F., Daniel, V. et al. Daily regulation of serum and urinary hepcidin is not influenced by submaximal cycling exercise in humans with normal iron metabolism. Eur J Appl Physiol 106, 435–443 (2009). https://doi.org/10.1007/s00421-009-1031-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-009-1031-8

Keywords

Navigation