Skip to main content
SpringerLink
Log in

Leptin signaling in skeletal muscle after bed rest in healthy humans

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

Abstract

Purpose

This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system.

Methods

Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m2) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot.

Results

After bed rest basal insulin concentration was increased by 53 % (P < 0.05), the homeostasis model assessment (HOMA) by 40 % (P < 0.05), and serum leptin concentration by 35 % (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90 % with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest.

Conclusions

One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AMPK 5′:

Adenosine monophosphate-activated protein kinase

AUC:

Area under curve

BMI:

Body mass index

DEXA:

Dual-energy X-ray absorbtiometry

ELISA:

Enzyme-linked immunosorbent assay

FLI:

Molar excess of leptin over s-OBR

HOMA:

Homeostatic model assessment of insulin resistance

JAK2:

Janus kinase 2

OB-R128:

Leptin receptor isoform of 128 kDa

OB-R170:

Leptin receptor isoform of 170 kDa

OB-R98:

Leptin receptor isoform of 98 kDa

OB-Rb:

Long isoform of the leptin receptor

OB-Rs:

Leptin receptor isoforms

OGTT:

Oral glucose tolerance test

PTP1B:

Protein tyrosine phosphatase 1B

SIRT1:

Sirtuin 1

s-OBR:

Soluble isoform of the leptin receptor

SOCS3:

Suppressor of cytokine signaling 3

STAT3:

Signal transducer and activator of transcription 3

TBS-T:

Tris-buffered saline with 0.1 % Tween 20

VO2max :

Maximal oxygen consumption or maximal oxygen uptake

References

  • Aas AM, Hanssen KF, Berg JP, Thorsby PM, Birkeland KI (2009) Insulin-stimulated increase in serum leptin levels precedes and correlates with weight gain during insulin therapy in type 2 diabetes. J Clin Endocrinol Metab 94:2900–2906

    Article  CAS  PubMed  Google Scholar 

  • Ahmad F, Azevedo JL, Cortright R, Dohm GL, Goldstein BJ (1997a) Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes. J Clin Invest 100:449–458

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ahmad F, Considine RV, Bauer TL, Ohannesian JP, Marco CC, Goldstein BJ (1997b) Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein-tyrosine phosphatases in adipose tissue. Metabolism 46:1140–1145

    Article  CAS  PubMed  Google Scholar 

  • Akira S (2000) Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 19:2607–2611

    Article  CAS  PubMed  Google Scholar 

  • Allen DL, Cleary AS, Speaker KJ, Lindsay SF, Uyenishi J, Reed JM, Madden MC, Mehan RS (2008) Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab 294:E918–E927

    Article  CAS  PubMed  Google Scholar 

  • Amati F (2012) Revisiting the diacylglycerol-induced insulin resistance hypothesis. Obes Rev 13(Suppl 2):40–50

    Article  CAS  PubMed  Google Scholar 

  • Ara I, Perez-Gomez J, Vicente-Rodriguez G, Chavarren J, Dorado C, Calbet JA (2006) Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme. Br J Nutr 96:1053–1059

    Article  CAS  PubMed  Google Scholar 

  • Arounleut P, Bowser M, Upadhyay S, Shi XM, Fulzele S, Johnson MH, Stranahan AM, Hill WD, Isales CM, Hamrick MW (2013) Absence of functional leptin receptor isoforms in the POUND (Lepr(db/lb)) mouse is associated with muscle atrophy and altered myoblast proliferation and differentiation. PLoS ONE 8:e72330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E, Neel BG, Schwartz MW, Myers MG Jr (2003) STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421:856–859

    Article  CAS  PubMed  Google Scholar 

  • Bienso RS, Ringholm S, Kiilerich K, Aachmann-Andersen NJ, Krogh-Madsen R, Guerra B, Plomgaard P, van Hall G, Treebak JT, Saltin B, Lundby C, Calbet JA, Pilegaard H, Wojtaszewski JF (2012) GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance. Diabetes 61:1090–1099

    Article  PubMed  Google Scholar 

  • Biolo G, Agostini F, Simunic B, Sturma M, Torelli L, Preiser JC, Deby-Dupont G, Magni P, Strollo F, di Prampero P, Guarnieri G, Mekjavic IB, Pisot R, Narici MV (2008) Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest. Am J Clin Nutr 88:950–958

    CAS  PubMed  Google Scholar 

  • Bjørbæk C, Kahn BB (2004) Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res 59:305–331

    Article  PubMed  Google Scholar 

  • Bjørbæk C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG Jr (2000) SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 275:40649–40657

    Article  Google Scholar 

  • Blanc S, Normand S, Pachiaudi C, Duvareille M, Gharib C (2000) Leptin responses to physical inactivity induced by simulated weightlessness. Am J Physiol Regul Integr Comp Physiol 279:R891–R898

    CAS  PubMed  Google Scholar 

  • Bosutti A, Malaponte G, Zanetti M, Castellino P, Heer M, Guarnieri G, Biolo G (2008) Calorie restriction modulates inactivity-induced changes in the inflammatory markers C-reactive protein and pentraxin-3. J Clin Endocrinol Metab 93:3226–3229

    Article  CAS  PubMed  Google Scholar 

  • Chan JL, Bluher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS (2002) Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Diabetes 51:2105–2112

    Article  CAS  PubMed  Google Scholar 

  • Chen YW, Gregory CM, Scarborough MT, Shi R, Walter GA, Vandenborne K (2007) Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics 31:510–520

    Article  CAS  PubMed  Google Scholar 

  • Cheng A, Uetani N, Simoncic PD, Chaubey VP, Lee-Loy A, McGlade CJ, Kennedy BP, Tremblay ML (2002) Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell 2:497–503

    Article  CAS  PubMed  Google Scholar 

  • Cheung A, Kusari J, Jansen D, Bandyopadhyay D, Kusari A, Bryer-Ash M (1999) Marked impairment of protein tyrosine phosphatase 1B activity in adipose tissue of obese subjects with and without type 2 diabetes mellitus. J Lab Clin Med 134:115–123

    Article  CAS  PubMed  Google Scholar 

  • Dela F, Helge JW (2013) Insulin resistance and mitochondrial function in skeletal muscle. Int J Biochem Cell Biol 45:11–15

    Article  CAS  PubMed  Google Scholar 

  • Dube N, Tremblay ML (2005) Involvement of the small protein tyrosine phosphatases TC-PTP and PTP1B in signal transduction and diseases: from diabetes, obesity to cell cycle, and cancer. Biochim Biophys Acta 1754:108–117

    Article  CAS  PubMed  Google Scholar 

  • Eckardt K, Taube A, Eckel J (2011) Obesity-associated insulin resistance in skeletal muscle: role of lipid accumulation and physical inactivity. Rev Endocr Metab Disord 12:163–172

    Article  CAS  PubMed  Google Scholar 

  • Eguchi M, Gillis LC, Liu Y, Lyakhovsky N, Du M, McDermott JC, Sweeney G (2007) Regulation of SOCS-3 expression by leptin and its co-localization with insulin receptor in rat skeletal muscle cells. Mol Cell Endocrinol 267:38–45

    Article  CAS  PubMed  Google Scholar 

  • Elia M, Stratton R, Stubbs J (2003) Techniques for the study of energy balance in man. Proc Nutr Soc 62:529–537

    Article  PubMed  Google Scholar 

  • Fuentes T, Ara I, Guadalupe-Grau A, Larsen S, Stallknecht B, Olmedillas H, Santana A, Helge JW, Calbet JA, Guerra B (2010) Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance. Exp Physiol 95:160–171

    Article  CAS  PubMed  Google Scholar 

  • Guerra B, Santana A, Fuentes T, Delgado-Guerra S, Cabrera-Socorro A, Dorado C, Calbet JA (2007) Leptin receptors in human skeletal muscle. J Appl Physiol 102:1786–1792

    Article  CAS  PubMed  Google Scholar 

  • Guerra B, Fuentes T, Delgado-Guerra S, Guadalupe-Grau A, Olmedillas H, Santana A, Ponce-Gonzalez JG, Dorado C, Calbet JA (2008) Gender dimorphism in skeletal muscle leptin receptors, serum leptin and insulin sensitivity. PLoS ONE 3:e3466

    Article  PubMed Central  PubMed  Google Scholar 

  • Hamrick MW, Herberg S, Arounleut P, He HZ, Shiver A, Qi RQ, Zhou L, Isales CM, Mi QS (2010) The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice. Biochem Biophys Res Commun 400:379–383

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Helge JW, Stallknecht B, Drachmann T, Hellgren LI, Jimenez-Jimenez R, Andersen JL, Richelsen B, Bruun JM (2011) Improved glucose tolerance after intensive life style intervention occurs without changes in muscle ceramide or triacylglycerol in morbidly obese subjects. Acta Physiol (Oxf) 201:357–364

    Article  CAS  Google Scholar 

  • Hikita M, Bujo H, Hirayama S, Takahashi K, Morisaki N, Saito Y (2000) Differential regulation of leptin receptor expression by insulin and leptin in neuroblastoma cells. Biochem Biophys Res Commun 271:703–709

    Article  CAS  PubMed  Google Scholar 

  • Hilton LK, Loucks AB (2000) Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women. Am J Physiol Endocrinol Metab 278:E43–E49

    CAS  PubMed  Google Scholar 

  • Hosoi T, Sasaki M, Miyahara T, Hashimoto C, Matsuo S, Yoshii M, Ozawa K (2008) Endoplasmic reticulum stress induces leptin resistance. Mol Pharmacol 74:1610–1619

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen SB, O’Neill HM, Sylow L, Honeyman J, Hewitt KA, Palanivel R, Fullerton MD, Oberg L, Balendran A, Galic S, van der Poel C, Trounce IA, Lynch GS, Schertzer JD, Steinberg GR (2013) Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes 62:56–64

    Article  CAS  PubMed  Google Scholar 

  • Judd LM, Bredin K, Kalantzis A, Jenkins BJ, Ernst M, Giraud AS (2006) STAT3 activation regulates growth, inflammation, and vascularization in a mouse model of gastric tumorigenesis. Gastroenterology 131:1073–1085

    Article  CAS  PubMed  Google Scholar 

  • Kiilerich K, Ringholm S, Bienso RS, Fisher JP, Iversen N, van Hall G, Wojtaszewski JF, Saltin B, Lundby C, Calbet JA, Pilegaard H (2011) Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest. J Appl Physiol 111:751–757

    Article  CAS  PubMed  Google Scholar 

  • Krawczewski Carhuatanta KA, Demuro G, Tschop MH, Pfluger PT, Benoit SC, Obici S (2011) Voluntary exercise improves high-fat diet-induced leptin resistance independent of adiposity. Endocrinology 152:2655–2664

    Article  PubMed  Google Scholar 

  • Krogh-Madsen R, Thyfault JP, Broholm C, Mortensen OH, Olsen RH, Mounier R, Plomgaard P, van Hall G, Booth FW, Pedersen BK (2010) A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity. J Appl Physiol 108:1034–1040

    Article  CAS  PubMed  Google Scholar 

  • Kusari J, Kenner KA, Suh KI, Hill DE, Henry RR (1994) Skeletal muscle protein tyrosine phosphatase activity and tyrosine phosphatase 1B protein content are associated with insulin action and resistance. J Clin Invest 93:1156–1162

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Laimer M, Ebenbichler CF, Kaser S, Sandhofer A, Weiss H, Nehoda H, Aigner F, Patsch JR (2002) Weight loss increases soluble leptin receptor levels and the soluble receptor bound fraction of leptin. Obes Res 10:597–601

    Article  CAS  PubMed  Google Scholar 

  • Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J (2001) Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun 283:982–988

    Article  CAS  PubMed  Google Scholar 

  • Liu ZJ, Endoh A, Li R, Ohzeki T (2004) Effects of leptin and dexamethasone on long and short leptin receptor mRNA. Pediatr Int 46:561–564

    Article  CAS  PubMed  Google Scholar 

  • Malmstrom R, Taskinen MR, Karonen SL, Yki-Jarvinen H (1996) Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM. Diabetologia 39:993–996

    Article  CAS  PubMed  Google Scholar 

  • Murphy JC, McDaniel JL, Mora K, Villareal DT, Fontana L, Weiss EP (2012) Preferential reductions in intermuscular and visceral adipose tissue with exercise-induced weight loss compared with calorie restriction. J Appl Physiol (1985) 112:79–85

    Article  Google Scholar 

  • Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH (1999) The disease burden associated with overweight and obesity. JAMA 282:1523–1529

    Article  CAS  PubMed  Google Scholar 

  • Myers MG, Cowley MA, Munzberg H (2008) Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 70:537–556

    Article  CAS  PubMed  Google Scholar 

  • Olmedillas H, Sanchis-Moysi J, Fuentes T, Guadalupe-Grau A, Ponce-Gonzalez JG, Morales-Alamo D, Santana A, Dorado C, Calbet JA, Guerra B (2010) Muscle hypertrophy and increased expression of leptin receptors in the musculus triceps brachii of the dominant arm in professional tennis players. Eur J Appl Physiol 108:749–758

    Article  CAS  PubMed  Google Scholar 

  • Olmedillas H, Guerra B, Guadalupe-Grau A, Santana A, Fuentes T, Dorado C, Serrano-Sanchez JA, Calbet JA (2011) Training, leptin receptors and SOCS3 in human muscle. Int J Sports Med 32:319–326

    Article  CAS  PubMed  Google Scholar 

  • Olsen DB, Sacchetti M, Dela F, Ploug T, Saltin B (2005) Glucose clearance is higher in arm than leg muscle in type 2 diabetes. J Physiol 565:555–562

    Article  CAS  PubMed  Google Scholar 

  • Pedersen BK (2007) Body mass index-independent effect of fitness and physical activity for all-cause mortality. Scand J Med Sci Sports 17:196–204

    Article  CAS  PubMed  Google Scholar 

  • Remesar X, Rafecas I, Fernandez-Lopez JA, Alemany M (1997) Is leptin an insulin counter-regulatory hormone? FEBS Lett 402:9–11

    Article  CAS  PubMed  Google Scholar 

  • Ringholm S, Bienso RS, Kiilerich K, Guadalupe-Grau A, Aachmann-Andersen NJ, Saltin B, Plomgaard P, Lundby C, Wojtaszewski JF, Calbet JA, Pilegaard H (2011) Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle. Am J Physiol Endocrinol Metab 301:E649–E658

    Article  CAS  PubMed  Google Scholar 

  • Saad MF, Khan A, Sharma A, Michael R, Riad-Gabriel MG, Boyadjian R, Jinagouda SD, Steil GM, Kamdar V (1998) Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544–549

    Article  CAS  PubMed  Google Scholar 

  • Sainz N, Rodriguez A, Catalan V, Becerril S, Ramirez B, Gomez-Ambrosi J, Fruhbeck G (2009) Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS ONE 4:e6808

    Article  PubMed Central  PubMed  Google Scholar 

  • Schaab M, Kausch H, Klammt J, Nowicki M, Anderegg U, Gebhardt R, Rose-John S, Scheller J, Thiery J, Kratzsch J (2012) Novel regulatory mechanisms for generation of the soluble leptin receptor: implications for leptin action. PLoS ONE 7:e34787

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  CAS  PubMed  Google Scholar 

  • Speakman JR, Westerterp KR (2010) Associations between energy demands, physical activity, and body composition in adult humans between 18 and 96 y of age. Am J Clin Nutr 92:826–834

    Article  CAS  PubMed  Google Scholar 

  • Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ (2002) Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 283:E187–E192

    CAS  PubMed  Google Scholar 

  • Steinberg GR, Smith AC, Wormald S, Malenfant P, Collier C, Dyck DJ (2004) Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle. Am J Physiol Endocrinol Metab 286:E57–E63

    Article  CAS  PubMed  Google Scholar 

  • Steinberg GR, McAinch AJ, Chen MB, O’Brien PE, Dixon JB, Cameron-Smith D, Kemp BE (2006) The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab 91:3592–3597

    Article  CAS  PubMed  Google Scholar 

  • Stepkowski SM, Chen W, Ross JA, Nagy ZS, Kirken RA (2008) STAT3: an important regulator of multiple cytokine functions. Transplantation 85:1372–1377

    Article  CAS  PubMed  Google Scholar 

  • St-Pierre J, Tremblay ML (2012) Modulation of leptin resistance by protein tyrosine phosphatases. Cell Metab 15:292–297

    Article  CAS  PubMed  Google Scholar 

  • Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q (2007) SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab 6:307–319

    Article  CAS  PubMed  Google Scholar 

  • Sun Q, van Dam RM, Meigs JB, Franco OH, Mantzoros CS, Hu FB (2010) Leptin and soluble leptin receptor levels in plasma and risk of type 2 diabetes in U.S. women: a prospective study. Diabetes 59:611–618

    Article  CAS  PubMed  Google Scholar 

  • van Dielen FM, van ‘t Veer C, Buurman WA, Greve JW (2002) Leptin and soluble leptin receptor levels in obese and weight-losing individuals. J Clin Endocrinol Metab 87:1708–1716

    Google Scholar 

  • Wang Z, Zhou YT, Kakuma T, Lee Y, Kalra SP, Kalra PS, Pan W, Unger RH (2000) Leptin resistance of adipocytes in obesity: role of suppressors of cytokine signaling. Biochem Biophys Res Commun 277:20–26

    Article  CAS  PubMed  Google Scholar 

  • Wolsk E, Mygind H, Grondahl TS, Pedersen BK, van Hall G (2011) The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males. Am J Clin Nutr 94:1533–1544

    Article  CAS  PubMed  Google Scholar 

  • Worm D, Vinten J, Beck-Nielsen H (1999) The significance of phosphotyrosine phosphatase (PTPase) 1B in insulin signalling. Diabetologia 42:1146–1149

    Article  CAS  PubMed  Google Scholar 

  • Yang G, Ge H, Boucher A, Yu X, Li C (2004) Modulation of direct leptin signaling by soluble leptin receptor. Mol Endocrinol 18:1354–1362

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Hulver M, McMillan RP, Cai L, Kershaw EE, Yu L, Xue B, Shi H (2012) Regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (SOCS3). PLoS ONE 7:e47493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zabolotny JM, Haj FG, Kim YB, Kim HJ, Shulman GI, Kim JK, Neel BG, Kahn BB (2004) Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action. J Biol Chem 279:24844–24851

    Article  CAS  PubMed  Google Scholar 

  • Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, Kahn BB (2008) Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem 283:14230–14241

    Article  CAS  PubMed  Google Scholar 

  • Zastrow O, Seidel B, Kiess W, Thiery J, Keller E, Bottner A, Kratzsch J (2003) The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes Relat Metab Disord 27:1472–1478

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Scarpace PJ (2009) The soluble leptin receptor neutralizes leptin-mediated STAT3 signalling and anorexic responses in vivo. Br J Pharmacol 158:475–482

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Chen Y, Heiman M, Dimarchi R (2005) Leptin: structure, function and biology. Vitam Horm 71:345–372

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the subjects for the extraordinary effort and the whole COPENHAGEN BED REST 2008 TEAM for excellent collaboration. Special thanks are given to José Navarro de Tuero for his excellent technical assistance. This study was supported by grants from the Lundbeck Foundation, Denmark, and The Danish Medical Research Council, Denmark, and the Ministerio de Ciencia e Innovación (BFU2006-13784 and FEDER) and FUNCIS (PI/10/07). Borja Guerra was a fellow of the “Recursos Humanos y Difusión de la Investigación” Program (Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain). The Centre of Inflammation and Metabolism (CIM) is supported by a grant from the Danish National Research Foundation (#02-512-55). The Copenhagen Muscle Research Centre is supported by a grant from the Capital Region of Denmark. CIM is part of the UNIK Project: Food, Fitness & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology and Innovation.

Conflict of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing the paper.

Author information

Authors and Affiliations

  1. Departamento de Educación Física, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira, 35017, Las Palmas de Gran Canaria, Canary Island, Spain

    Borja Guerra, Jesus Gustavo Ponce-González, David Morales-Alamo, Amelia Guadalupe-Grau, Teresa Fuentes, Alfredo Santana & José A. L. Calbet

  2. Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark

    Kristian Kiilerich, Stine Ringholm, Rasmus Sjørup Biensø & Henriette Pilegaard

  3. Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark

    Kristian Kiilerich, Stine Ringholm, Rasmus Sjørup Biensø & Henriette Pilegaard

  4. Department of Biology, August Krogh Building, University of Copenhagen, Copenhagen, Denmark

    Kristian Kiilerich, Stine Ringholm, Rasmus Sjørup Biensø & Henriette Pilegaard

  5. Clinical Genetics Unit, Childhood Hospital-Materno Infantil de Las Palmas, Avenida Marítima del Sur s/n, 35016, Las Palmas de Gran Canaria, Spain

    Alfredo Santana

  6. Research Unit, Hospital de Gran Canaria Dr. Negrín, Bco Ballena s/n, 35013, Las Palmas de Gran Canaria, Spain

    Alfredo Santana

  7. Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland

    Carsten Lundby

Authors
  1. Borja Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jesus Gustavo Ponce-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Morales-Alamo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amelia Guadalupe-Grau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kristian Kiilerich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Teresa Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stine Ringholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rasmus Sjørup Biensø
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alfredo Santana
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carsten Lundby
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Henriette Pilegaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. José A. L. Calbet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Borja Guerra.

Additional information

Communicated by Jean-René Lacour.

The human experiments were conducted at Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guerra, B., Ponce-González, J.G., Morales-Alamo, D. et al. Leptin signaling in skeletal muscle after bed rest in healthy humans. Eur J Appl Physiol 114, 345–357 (2014). https://doi.org/10.1007/s00421-013-2779-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-013-2779-4

Keywords

Search

Navigation