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Influence of exercise on the circulating levels and macrophage production of IL-1β and IFNγ affected by metabolic syndrome: an obese Zucker rat experimental animal model

Abstract

Regular physical activity is recognized as a non-pharmacological treatment of genetic obesity and type-II diabetes, and based on the “anti-inflammatory” effects of exercise, it has been also proposed for improving the “chronic low-grade inflammation” in metabolic syndrome (MS). The aim of the present work was to evaluate the effects of an habitual exercise program (running, 5 days/week for 35 min at 35 cm/s for 14 weeks) and of a bout of acute exercise (running, for 35 min at 35 cm/s) on MS-associated disorders in the pro-inflammatory cytokines IL-1β and IFNγ. The study was carried out on obese Zucker rats (fa/fa). The obese rats presented higher circulating concentrations and constitutive macrophage production (in the absence of antigenic stimulus) of IL-1β (but not of IFNγ). But their production of both IL-1β and IFNγ by lipopolysaccharide (LPS)-stimulated macrophages was lower than that of the control lean rats. Our protocol of exercise training did not modify the circulating concentration and constitutive macrophage release of either IL-1β or IFNγ in the obese rats, but increased the production of both cytokines by LPS-stimulated macrophages. The single bout of acute exercise only increased the release of IL-1β by the LPS-stimulated macrophages from obese rats, in both sedentary and trained animals. The results indicated that: (1) circulating levels and constitutive production of IL-1β by macrophages are deregulated in rats with MS, and (2) IL-1β and IFNγ production by macrophages in response to antigenic stimulus (LPS) is impaired in the obese animals, and this MS-associated disorder is improved by the program of habitual exercise training.

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References

  • Bassuk SS, Manson JE (2005) Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol 99:1193–1204

    Article  PubMed  Google Scholar 

  • Bouloumié A, Curat CA, Sengenès C, Lolmède K, Miranville A, Busse R (2005) Role of macrophage tissue infiltration in metabolic diseases. Curr Opin Clin Nutr Metab Care 8:347–354

    Article  PubMed  Google Scholar 

  • Bruce CR, Kriketos AD, Cooney GJ, Hawley JA (2004) Disassociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with type 2 diabetes. Diabetologia 47:23–30

    Article  CAS  PubMed  Google Scholar 

  • Das UN (2001) Is obesity an inflammatory condition? Nutrition 17:9539–9566

    Google Scholar 

  • Das UN (2002) Is metabolic syndrome X an inflammatory condition? Exp Biol Med 227:989–997

    CAS  Google Scholar 

  • De Lemos ET, Reis F, Baptista S, Pinto R, Sepodes B, Vala H, Rocha-Pereira P, Silva AS, Teixeira F (2007) Exercise training is associated with improved levels of C-reactive protein and adiponectin in ZDF (type 2) diabetic rats. Med Sci Monit 13:168–174

    Google Scholar 

  • Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428

    Article  CAS  PubMed  Google Scholar 

  • Elenkov IJ, Chrousos GP (2002) Stress hormones, proinflammatory and anti-inflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 966:290–303

    Article  CAS  PubMed  Google Scholar 

  • Forner MA, Collazos ME, Barriga C, De la Fuente M, Rodríguez AB, Ortega E (1994) Effect of age on adherence and chemotaxis capacities of peritoneal macrophages. Influence of physical activity stress. Mech Ageing and Dev 75:179–189

    Article  CAS  Google Scholar 

  • Forner MA, Barriga C, Rodríguez AB, Ortega E (1995) A study of the role of corticosterone as a mediator in exercise-induced stimulation of murine macrophage phagocytosis. J Physiol 488:789–794

    CAS  PubMed  Google Scholar 

  • Giraldo E, Hinchado MD, Garcia JJ, Ortega E (2008) Influence of gender and oral contraceptives intake on innate and inflammatory response. Role of neuroendocrine factors. Mol Cell Biochem 313:147–153

    Article  CAS  PubMed  Google Scholar 

  • Gleeson M (2007) Immune function in sport and exercise. J Appl Physiol 103:693–699

    Article  CAS  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 40:23–29

    Article  CAS  PubMed  Google Scholar 

  • Hansen BC (1999) The metabolic syndrome X. Ann N Y Acad Sci 892:1–24

    Article  CAS  PubMed  Google Scholar 

  • Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Investig 95:2409–2415

    Article  CAS  PubMed  Google Scholar 

  • Ito Y, Daitoku H, Fukamizu A (2009) Foxo1 increases pro-inflammatory gene expression by inducing C/EBPbeta in TNF-alpha-treated adipocytes. Biochem Biophys Res Commun 378:290–295

    Article  CAS  PubMed  Google Scholar 

  • Klimcakova E, Polak J, Moro C, Hejnova J, Majercik M, Viguerie N, Berlan M, Langin D, Stich V (2006) Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men. J Clin Endocrinol Metab 91:5107–5112

    Article  CAS  PubMed  Google Scholar 

  • Koh KK, Han SH, Quon MJ (2005) Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 46:1978–1985

    Article  CAS  PubMed  Google Scholar 

  • Mathur N, Pedersen BK (2008) Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm doi:10.1155/2008/109502

  • Odrowaz-Sypniewska G (2007) Markers of pro-inflammatory and pro-thrombotic state in the diagnosis of metabolic syndrome. Adv Med Sci 52:246–250

    CAS  PubMed  Google Scholar 

  • Ortega E (1994) Physiological and biochemistry: influence of exercise on phagocytosis. Int J Sports Med 15:5172–5178

    Google Scholar 

  • Ortega E (2003) Neuroendocrine mediators in the modulation of phagocytosis by exercise: physiological implications. Exerc Immunol Rev 9:70–94

    PubMed  Google Scholar 

  • Ortega E, Collazos ME, Barriga C, De la Fuente M (1992a) Effect of physical activity stress on the phagocytic process of peritoneal macrophages from old guinea pigs. Mech Ageing Dev 65:157–165

    Article  CAS  PubMed  Google Scholar 

  • Ortega E, Collazos ME, Barriga C, De la Fuente M (1992b) Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress. Eur J Appl Physiol Occup Physiol 64:323–327

    Article  CAS  PubMed  Google Scholar 

  • Ortega E, Forner MA, Barriga C (1997) Exercise-induced stimulation of murine macrophage chemotaxis: role of corticosterone and prolactin as mediators. J Physiol 498:729–734

    CAS  PubMed  Google Scholar 

  • Ortega E, Garcia JJ, De La Fuente M (2000) Ageing modulates some aspects of the non-specific immune response of murine macrophages and lymphocytes. Exp Physiol 85:519–525

    Article  CAS  PubMed  Google Scholar 

  • Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) The cytokine balance and strenuous exercise: TNFalpha, IL-2beta, IL-6, IL-1ra, sTNF-r1, sTNF-r2, and IL-10. J Physiol 515:287–291

    Article  CAS  PubMed  Google Scholar 

  • Pedersen BK (2006) The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem 42:105–117

    Article  CAS  PubMed  Google Scholar 

  • Permana PA, Menge C, Reaven PD (2006) Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 341:507–514

    Article  CAS  PubMed  Google Scholar 

  • Petersen AM, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol 98:1154–1162

    Article  CAS  PubMed  Google Scholar 

  • Pickavance L, Tadayyon M, Williams G, Vernon RG (1998) Lactation suppresses diurnal rhythm of serum leptin. Biochem Biophys Res Commun 248:196–199

    Article  CAS  PubMed  Google Scholar 

  • Pischon T, Hu FB, Rexrode KM, Girman CJ, Manson JE, Rimm EB (2008) Inflammation, the metabolic syndrome, and risk of coronary heart disease in women and men. Atherosclerosis 197:392–399

    Article  CAS  PubMed  Google Scholar 

  • Pitsavos C, Panagiotakos DB, Chrysohoou C, Kavouras S, Stefanadis C (2005) The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study. Eur J Cardiovasc Prev Rehabil 12:151–158

    Article  PubMed  Google Scholar 

  • Ritchie SA, Connell JM (2007) The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis 17:319–326

    Article  CAS  PubMed  Google Scholar 

  • Roberts CK, Barnard RJ (2005) Effects of exercise and diet on chronic disease. J Appl Physiol 98:3–30

    Article  PubMed  Google Scholar 

  • Roberts CK, Won D, Pruthi S, Kurtovic S, Sindhu RK, Vaziri ND, Barnard RJ (2006) Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. J Appl Physiol 100:1657–1665

    Article  CAS  PubMed  Google Scholar 

  • Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Investig 116:1793–1801

    Article  CAS  PubMed  Google Scholar 

  • Teixeira de Lemos E, Reis F, Baptista S, Pinto R, Sepodes B, Vala H, Rocha-Pereira P, Correia da Silva G, Teixeira N, Silva AS, Carvalho L, Teixeira F, Das UN (2008) Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats. Nutrition 25:330–339

    Article  PubMed  Google Scholar 

  • Trøseid M, Lappegård KT, Claudi T, Damås JK, Mørkrid L, Brendberg R, Mollnes TE (2004) Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur Heart J 25:349–355

    Article  PubMed  Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig 112:1796–1808

    CAS  PubMed  Google Scholar 

  • Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Investig 112:1785–1788

    CAS  PubMed  Google Scholar 

  • Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Investig 115:1111–1119

    CAS  PubMed  Google Scholar 

  • Xiang L, Naik J, Hester RL (2005) Exercise-induced increase in skeletal muscle vasodilatory responses in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 288:987–991

    Google Scholar 

  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity related insulin resistance. J Clin Investig 112:1821–1830

    CAS  PubMed  Google Scholar 

  • Zimmet P, George K, Alberti MM, Serrano M (2005) Una nueva definición mundial del síndrome metabólico propuesta por la Federación Internacional de Diabetes: fundamento y resultados. Rev Esp Cardiol 58:1371–1376

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was partially supported by grants DEP2006-56187-C04-03 (Ministry of Science and Innovation), GRU08039 (Junta de Extremadura) and Fundación Valhondo de Extremadura, Spain. The experiment was approved by the Ethical Committees of the Autonoma University (Madrid, Spain) and of the University of Extremadura (Badajoz, Spain) according to the guidelines of the European Community Council Directives and the Declaration of Helsinki.

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Correspondence to E. Ortega.

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Martin-Cordero, L., Garcia, J.J., Giraldo, E. et al. Influence of exercise on the circulating levels and macrophage production of IL-1β and IFNγ affected by metabolic syndrome: an obese Zucker rat experimental animal model. Eur J Appl Physiol 107, 535 (2009). https://doi.org/10.1007/s00421-009-1140-4

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  • DOI: https://doi.org/10.1007/s00421-009-1140-4

Keywords

  • Exercise
  • Metabolic syndrome
  • Obesity
  • Inflammation
  • Macrophages
  • Zucker rats