Skip to main content
SpringerLink
Log in

Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats

  • Original Paper
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.

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

Similar content being viewed by others

References

  • Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW et al (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6(4):435–442

    Article  CAS  PubMed  Google Scholar 

  • Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE et al (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034

    Article  CAS  PubMed  Google Scholar 

  • Atalay M, Oksala NK, Laaksonen DE, Khanna S, Nakao C, Lappalainen J et al (2004) Exercise training modulates heat shock protein response in diabetic rats. J Appl Physiol (1985) 97(2):605–611

    Article  CAS  Google Scholar 

  • Atalay M, Oksala N, Lappalainen J, Laaksonen DE, Sen CK, Roy S (2009) Heat shock proteins in diabetes and wound healing. Curr Protein Pept Sci 10(1):85–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batra A, Siegmund B (2012) The role of visceral fat. Dig Dis 30:70–74

    Article  PubMed  Google Scholar 

  • Bischoff R, Heintz C (1994) Enhancement of skeletal muscle regeneration. Dev Dyn 201(1):41–54

    Article  CAS  PubMed  Google Scholar 

  • Borges TJ, Wieten L, van Herwijnen MJ, Broere F, van der Zee R, Bonorino C et al (2012) The anti-inflammatory mechanisms of Hsp70. Front Immunol 3:95

    Article  PubMed  PubMed Central  Google Scholar 

  • Borges TJ, Lopes RL, Pinho NG, Machado FD, Souza AP, Bonorino C (2013) Extracellular Hsp70 inhibits pro-inflammatory cytokine production by IL-10 driven down-regulation of C/EBPβ and C/EBPδ. Int J Hyperth 29(5):455–463

    Article  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Burkart V, Germaschewski L, Schloot NC, Bellmann K, Kolb H (2008) Deficient heat shock protein 70 response to stress in leukocytes at onset of type 1 diabetes. Biochem Biophys Res Commun 369(2):421–425

    Article  CAS  PubMed  Google Scholar 

  • Cabrera SM, Henschel AM, Hessner MJ (2016) Innate inflammation in type 1 diabetes. Transl Res 167(1):214–227

    Article  CAS  PubMed  Google Scholar 

  • Calle MC, Fernandez ML (2010) Effects of resistance training on the inflammatory response. Nutr Res Pract 4(4):259–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coleman SK, Rebalka IA, D'Souza DM, Hawke TJ (2015) Skeletal muscle as a therapeutic target for delaying type 1 diabetic complications. World J Diabetes 6(17):1323–1336

    Article  PubMed  PubMed Central  Google Scholar 

  • Coppack SW (2001) Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 60(3):349–356

    Article  CAS  PubMed  Google Scholar 

  • Farrell PA, Fedele MJ, Hernandez J, Fluckey JD, Miller JL 3rd, Lang CH et al (1999) Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise. J Appl Physiol 87(3):1075–1082

    CAS  PubMed  Google Scholar 

  • Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 61:243–282

    Article  CAS  PubMed  Google Scholar 

  • Fischer CP, Hiscock NJ, Basu S, Vessby B, Kallner A, Sjoberg LB et al (2006) Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expressions in humans. J Appl Physiol 100:1679–1687

    Article  CAS  PubMed  Google Scholar 

  • Fitts RH, Widrick JJ (1996) Muscle mechanics: adaptations with exercise-training. Exerc Sport Sci Rev 24:427–473

    Article  CAS  PubMed  Google Scholar 

  • Frier BC, Locke M (2007) Heat stress inhibits skeletal muscle hypertrophy. Cell Stress Chaperones 12(2):132–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gjøvaag TF, Vikne H, Dahl HA (2006) Effect of concentric or eccentric weight training on the expression of heat shock proteins in m. biceps brachii of very well trained males. Eur J Appl Physiol 96:355–362

    Article  PubMed  Google Scholar 

  • Gomez-Merino D, Drogou C, Guezennec CY, Chennaoui M (2007) Effects of chronic exercise on cytokine production in white adipose tissue and skeletal muscle of rats. Cytokine 40(1):23–29

    Article  CAS  PubMed  Google Scholar 

  • Gruden G, Bruno G, Chaturvedi N, Burt D, Pinach S, Schalkwijk C et al (2009) ANTI-HSP60 and ANTI-HSP70 antibody levels and micro/macrovascular complications in type 1 diabetes: the EURODIAB Study. J Intern Med 266:527–536

    Article  CAS  PubMed  Google Scholar 

  • Gunawardana SC (2012) Adipose tissue, hormones, and treatment of type 1 diabetes. Curr Diab Rep 12(5):542–550

    Article  CAS  PubMed  Google Scholar 

  • Hansen D, Eijnde BO, Roelants M, Broekmans T, Rummens JL, Hensen K et al (2011) Clinical benefits of the addition of lower extremity low-intensity resistance muscle training to early aerobic endurance training intervention in patients with coronary artery disease: a randomized controlled trial. J Rehabil Med 43(9):800–807

    Article  PubMed  Google Scholar 

  • Hornberger TA Jr, Farrar RP (2004) Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Can J Appl Physiol 29(1):16–31

    Article  CAS  PubMed  Google Scholar 

  • Johnson JD, Fleshner M (2006) Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72. J Leukoc Biol 79:425–434

    Article  CAS  PubMed  Google Scholar 

  • Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280(5):E745–E751

    CAS  PubMed  Google Scholar 

  • Krause MP, Riddell MC, Hawke TJ (2011) Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr Diabetes 12(4 Pt 1):345–364

    Article  CAS  PubMed  Google Scholar 

  • Lago F, Dieguez C, Gomez-Reino J, Gualillo O (2007) Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 3:716–724

    Article  CAS  PubMed  Google Scholar 

  • Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S (2005) Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol 288(5):H2031–H2041

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Barton ER, Sweeney HL, Farrar RP (2004) Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats. J Appl Physiol 96(3):1097–1104

    Article  CAS  PubMed  Google Scholar 

  • Lee SL, Chen KW, Chen ST, Chu PJ, Chen CS, Hsu MC et al (2011) Effect of passive repetitive isokinetic training on cytokines and hormonal changes. Chin J Physiol 54(1):55–66

    Article  CAS  PubMed  Google Scholar 

  • Levinger I, Goodman C, Peake J, Garnham A, Hare DL, Jerums G et al (2009) Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors. Diabet Med 26(3):220–227

    Article  CAS  PubMed  Google Scholar 

  • Lira FS, Koyama CH, Yamashita AS, Rosa JC, Zanchi NE, Batista ML Jr et al (2009) Chronic exercise decreases cytokine production in healthy rat skeletal muscle. Cell Biochem Funct 27(7):458–461

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Lormes W, Wang L, Reissnecker S, Steinacker JM (2004) Different skeletal muscle HSP70 responses to high-intensity strength training and low-intensity endurance training. Eur J Appl Physiol 91:330–335

    Article  CAS  PubMed  Google Scholar 

  • Locke M, Noble EG, Atkinson BG (1991) Inducible isoform of Hsp70 is constitutively expressed in a muscle fiber type specific pattern. Am J Physiol Cell Physiol 261:C774–C779

    CAS  Google Scholar 

  • Malm C (2001) Exercise-induced muscle damage and inflammation: fact or fiction? Acta Physiol Scand 171(3):233–239

    Article  CAS  PubMed  Google Scholar 

  • Mardare C, Krüger K, Liebisch G, Seimetz M, Couturier A, Ringseis R et al (2016) Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice. J Diabetes Res 2016:4536470

    Article  PubMed  Google Scholar 

  • Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62(6):670–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molanouri Shamsi M, Hassan ZH, Gharakhanlou R, Quinn LS, Azadmanesh K, Baghersad L et al (2014) Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training. Endocrine 46(1):60–69

    Article  CAS  PubMed  Google Scholar 

  • Molanouri Shamsi M, Hassan ZM, Quinn LS, Gharakhanlou R, Baghersad L, Mahdavi M (2015) Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype. Endocrine 49(2):396–403

    Article  CAS  PubMed  Google Scholar 

  • Morton JP, MacLaren DP, Cable NT, Bongers T, GriYths RD, Campbell IT et al (2006) Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise. J Appl Physiol 101:176–182

    Article  CAS  PubMed  Google Scholar 

  • Morton JP, Kayani AC, McArdle A, Drust B (2009) The exercise induced stress response of skeletal muscle, with specific emphasis on humans. Sports Med 39:643–662

    Article  PubMed  Google Scholar 

  • Najemnikova E, Rodgers CD, Locke M (2007) Altered heat stress response following streptozotocin-induced diabetes. Cell Stress Chaperones Winter 12(4):342–352

    Article  CAS  Google Scholar 

  • Nakhjavani M, Morteza A, Khajeali L, Esteghamati A, Khalilzadeh O, Asgarani F et al (2010) Increased serum HSP70 levels are associated with the duration of diabetes. Cell Stress Chaperones 15(6):959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noble EG, Shen GX (2012) Impact of exercise and metabolic disorders on heat shock proteins and vascular inflammation. Autoimmune Dis 2012:836519

    PubMed  Google Scholar 

  • Ogata T, Oishi Y, Roy RR, Ohmori H (2005) Effects of T3 treatment on HSP72 and calcineurin content of functionally overloaded rat plantaris muscle. Biochem Biophys Res Commun 331:1317–1323

    Article  CAS  Google Scholar 

  • Oglesbee MJ, Herdman AV, Passmore GG, Hoffman WH (2005) Diabetic ketoacidosis increases extracellular levels of the major inducible 70-kDa heat shock protein. J Biomed Biotechnol 38:900–904

    CAS  Google Scholar 

  • O'Neill DE, Aubrey FK, Zeldin DA, Michel RN, Noble EG (2006) Slower skeletal muscle phenotypes are critical for constitutive expression of Hsp70 in overloaded rat plantaris muscle. J Appl Physiol (1985) 100(3):981–987

    Article  Google Scholar 

  • Ono T, Takada S, Kinugawa S, Tsutsui H (2015) Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination. Exp Physiol 100(9):1052–1063

    Article  CAS  PubMed  Google Scholar 

  • Paulsen G, Hanssen KE, Rønnestad BR, Kvamme NH, Ugelstad I, Kadi F et al (2012) Strength training elevates HSP27, HSP70 and αB-crystallin levels in musculi vastus lateralis and trapezius. Eur J Appl Physiol 112(5):1773–1782

    Article  CAS  PubMed  Google Scholar 

  • Phillips SM (2014) A brief review of critical processes in exercise-induced muscular hypertrophy. Sports Med 44(1):S71–S77

    Article  PubMed  Google Scholar 

  • Portha B, Blondel O, Serradas P, McEvoy R, Giroix MH, Kergoat M, Bailbe D (1989) The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin. Diabete Metab 15(2):61–75

    CAS  PubMed  Google Scholar 

  • Price JD, Tarbell KV (2015) The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases. Front Immunol 6:288

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosa Neto JC, Lira FS, Oyama LM, Zanchi NE, Yamashita AS, Batista ML Jr et al (2009) Exhaustive exercise causes an anti-inflammatory effect in skeletal muscle and a pro-inflammatory effect in adipose tissue in rats. Eur J Appl Physiol 106(5):697–704

    Article  CAS  PubMed  Google Scholar 

  • Russell ST, Rajani S, Dhadda RS, Tisdale MJ (2009) Mechanism of induction of muscle protein loss by hyperglycaemia. Exp Cell Res 315:16–25

    Article  CAS  PubMed  Google Scholar 

  • Rutschmann M, Dahlmann B, Reinauer H (1984) Loss of fast twitch isomyosins in skeletal muscles of the diabetic rat. Biochem J 221:645–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silver JT, Kowalchuk H, Noble EG (2012) hsp70 mRNA temporal localization in rat skeletal myofibers and blood vessels post-exercise. Cell Stress Chaperones 17(1):109–120

    Article  CAS  PubMed  Google Scholar 

  • Speaker KJ, Cox SS, Paton MM, Serebrakian A, Maslanik T, Greenwood BN, Fleshner M (2014) Six weeks of voluntary wheel running modulates inflammatory protein (MCP-1, IL-6, and IL-10) and DAMP (Hsp72) responses to acute stress in white adipose tissue of lean rats. Brain Behav Immun 39:87–98

    Article  CAS  PubMed  Google Scholar 

  • Steinacker JM, Lormes W, Reissnecker S, Liu Y (2004) New aspects of the hormone and cytokine response to training. Eur J Appl Physiol 91:382–391

    Article  CAS  PubMed  Google Scholar 

  • Takada J, Machado MA, Peres SB, Brito LC, Borges-Silva CN, Costa CE et al (2007) Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass. Metabolism 56(7):977–984

    Article  CAS  PubMed  Google Scholar 

  • Tupling AR, Bombardier E, Stewart RD, Vigna C, Aqui AE (2007) Muscle fiber type-specific response of Hsp70 expression in human quadriceps following acute isometric exercise. J Appl Physiol 103:2105–2111

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M et al (2012) Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1. Diabetes 61(6):1552–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Molle W, Wielockx B, Mahieu T, Takada M, Taniguchi T, Sekikawa K, Libert C (2002) HSP70 protects against TNF-induced lethal inflammatory shock. Immunity 16(5):685–695

    Article  PubMed  Google Scholar 

  • Vogt M, Puntschart A, Geiser J, Zuleger C, Billeter R, Hoppeler H (2001) Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions. J Appl Physiol 91:173–182

    CAS  PubMed  Google Scholar 

  • Wang Y, Pessin JE (2013) Mechanisms for fiber-type specificity of skeletal muscle atrophy. Curr Opin Clin Nutr Metab Care 16(3):243–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei W, Liu Q, Tan Y, Liu L, Li X, Cai L (2009) Oxidative stress, diabetes, and diabetic complications. Hemoglobin 33:370–377

    Article  CAS  PubMed  Google Scholar 

  • Westerheide SD, Morimoto RI (2005) Heat shock response modulators as therapeutic tools for diseases of protein conformation. J Biol Chem 280:33097–33100

    Article  CAS  PubMed  Google Scholar 

  • Wu D, Ren Z, Pae M, Guo W, Cui X, Merrill AH et al (2007) Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J Immunol 179(7):4829–4839

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto K, Takeshita K, Shimokawa T, Yi H, Isobe K, Loskutoff DJ et al (2002) Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals. Proc Natl Acad Sci U S A 99(2):890–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You T, Yang R, Lyles MF, Gong D, Nicklas BJ (2005) Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors. Am J Physiol Endocrinol Metab 288(4):E741–E747

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Research Center of Tarbiat Modarres University (TMU), Tehran, Iran. We wish to thank Professor Yaghob Fathoallahy for their kind help and sincere cooperation.

Author information

Authors and Affiliations

  1. Physical Education and Sport Sciences Dept., Faculty of Humanities, Tarbiat Modares University, Jala Ale Ahmad Exp., P.O.Box: 14117-13116, Tehran, Iran

    M. Molanouri Shamsi & R. Gharakhanlou

  2. Immunology Department, Pasteur Institute of Iran, 69 Pasteur Ave, Tehran, Iran

    M. Mahdavi

  3. Research Service, VA Puget Sound Health Care System, and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, 98108, USA

    L. S. Quinn

  4. Physical Education and Sport Sciences Dept., Faculty of Humanities, Shahed University, P.O.Box: 14117-13116, Tehran, I.R., Iran

    A. Isanegad

  5. Immunoregulation Research Center, Shahed University, P.O.Box: 14117-13116, Tehran, I.R., Iran

    A. Isanegad

Authors
  1. M. Molanouri Shamsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Mahdavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. S. Quinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Gharakhanlou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Isanegad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Molanouri Shamsi.

Ethics declarations

All experiments involving animals were conducted according to the policies of the Iranian Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes, and the protocol was approved by the Ethics Committee of the School of Medicine Sciences, Tarbiat Modares University (TMU), Tehran, Iran.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Molanouri Shamsi, M., Mahdavi, M., Quinn, L.S. et al. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats. Cell Stress and Chaperones 21, 783–791 (2016). https://doi.org/10.1007/s12192-016-0703-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-016-0703-7

Keywords

Search

Navigation