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Journal of Physiology and Biochemistry

, Volume 72, Issue 4, pp 643–656 | Cite as

Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis

  • Pauline Brendler Goettems-Fiorin
  • Bethânia Salamoni Grochanke
  • Fernanda Giesel Baldissera
  • Analu Bender dos Santos
  • Paulo Ivo Homem de BittencourtJr
  • Mirna Stela Ludwig
  • Claudia Ramos Rhoden
  • Thiago Gomes HeckEmail author
Original Paper

Abstract

Exposure to fine particulate matter (PM2.5) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM2.5 over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70-kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM2.5 for additional 12 weeks under the same diet schedule, divided into four groups (n = 14–15 each): Control, PM2.5, HFD, and HFD + PM2.5 were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues. Extracellular to intracellular HSP70 ratio ([eHSP72]/[iHSP70]), viz. H-index, was then calculated. HFD + PM2.5 mice presented a positive correlation between adiposity, increased body weight and glucose intolerance, and increased glucose and triacylglycerol plasma levels. Pancreas exhibited lower iHSP70 expression, accompanied by 3.7-fold increase in the plasma to pancreas [eHSP72]/[iHSP70] ratio. Exposure to PM2.5 markedly potentiated metabolic dysfunction in HFD-treated mice and promoted relevant alteration in cell stress response assessed by [eHSP72]/[iHSP70], a relevant biomarker of chronic low-grade inflammatory state and T2DM risk.

Keywords

Adiposity Particulate matter Glycemic control Heat shock protein HSP70 Blood glucose 

Abbreviations

CAT

Catalase

CD91

α2-Macroglobulin receptor

DM

Diabetes mellitus

EWAT

Epididymal white adipose tissue

GTT

Glucose tolerance test

HFD

High-fat diet

HSP70

The 70-kDa family of heat shock proteins

eHSP70

Extracellular 70-kDa heat shock proteins

iHSP70

Intracellular 70-kDa heat shock proteins

IAUC

Incremental area under the curve

NF-kB

Nuclear factor-kappa B

NMRT

Nutrient metabolism-related tissues

PM

Particulate matter

PM2.5

Fine particulate matter

PMSF

Phenylmethanesulfonyl fluoride

SDS

Sodium dodecyl sulfate

SOD

Superoxide dismutase

T2DM

Type 2 diabetes

TLCK

Tosyl-l-lysine chloromethyl ketone hydrochloride

TLR2

Toll-like receptor 2

TLR4

Toll-like receptor 4

Notes

Acknowledgments

The authors would like to thank to E.G.P. Basso, E.T.C. Martins, M.M. Sulzbacher, R.D.B. Basso (all from UNIJUI), P.H.N. Saldiva (USP), and colleagues from the Laboratory of Oxidative Stress and Atmospheric Pollution (UFCSPA) for their technical support.

Author contribution

PBGF completed all the experiments described in this manuscript. PBGF, BS, and FGB performed biometric and metabolic profile. PBGF and ABS performed experiments on oxidative stress parameters. PBGF, BS, and FGB performed Western blot analyses. All authors were involved in analyzing the results. PBGF, TGH, and MSL co-wrote the paper. TGH and CRR designed the study. PIHBJ, TGH, MSL, and CRR provided experimental advice and helped with manuscript revision. All the authors had final approval of the submitted and published versions.

Compliance with ethical standards

Competing interest

The authors declare that they do not have competing financial interests.

Financial support

This work was supported by Federal University of Health Sciences of Porto Alegre (UFCSPA) and by grants from Research Support Foundation of the State of Rio Grande do Sul (PqG-2013 - FAPERGS, process: 002106-2551/13-5 to TGH). PBGF and FGB were recipients of scholarships from the Coordination for the Improvement of Higher Education Personnel (CAPES) and ABS from Research Support Foundation of the State of Rio Grande do Sul (FAPERGS).

References

  1. 1.
    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefPubMedGoogle Scholar
  2. 2.
    Bock PM, Krause M, Schroeder HT, Hahn GF, Takahashi HK, Scholer CM, Nicoletti G, Neto LD, Rodrigues MI, Bruxel MA et al (2016) Oral supplementations with L-glutamine or L-alanyl-L-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance. Mol Cell Biochem 411:351–362CrossRefPubMedGoogle Scholar
  3. 3.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  4. 4.
    Chen JC, Schwartz J (2008) Metabolic syndrome and inflammatory responses to long-term particulate air pollutants. Environ Health Perspect 116:612–617CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Defronzo RA (2009) Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773–795CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Di Naso FC, Porto RR, Fillmann HS, Maggioni L, Padoin AV, Ramos RJ, Mottin CC, Bittencourt A, Marroni NA, de Bittencourt HPI Jr (2015) Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression. Obesity 23:120–129CrossRefPubMedGoogle Scholar
  7. 7.
    Emmerechts J, Hoylaerts MF (2012) The effect of air pollution on haemostasis. Hamostaseologie 32:5–13CrossRefPubMedGoogle Scholar
  8. 8.
  9. 9.
    Fajersztajn L, Veras M, Barrozo LV, Saldiva P (2013) Air pollution: a potentially modifiable risk factor for lung cancer. Nat Rev Cancer 13:674–678CrossRefPubMedGoogle Scholar
  10. 10.
    Heck TG, Scholer CM, de Bittencourt HPI Jr (2011) HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain? Cell Biochem Funct 29:215–226CrossRefPubMedGoogle Scholar
  11. 11.
    Hoffmann B, Moebus S, Dragano N, Stang A, Mohlenkamp S, Schmermund A, Memmesheimer M, Brocker-Preuss M, Mann K, Erbel R et al (2009) Chronic residential exposure to particulate matter air pollution and systemic inflammatory markers. Environ Health Perspect 117:1302–1308CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hooper PL, Balogh G, Rivas E, Kavanagh K, Vigh L (2014) The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes. Cell Stress Chaperones 19:447–464CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kang R, Lotze MT, Zeh HJ, Billiar TR, Tang D (2014) Cell death and DAMPs in acute pancreatitis. Mol Med 20:466–477CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Keane KN, Cruzat VF, Carlessi R, de Bittencourt PI H Jr, Newsholme P (2015) Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and beta-Cell Dysfunction. Oxidative Med Cell Longev 2015:181643CrossRefGoogle Scholar
  15. 15.
    Kolberg A, Rosa TG, Puhl MT, Scola G, da Rocha JD, Maslinkiewicz A, Lagranha DJ, Heck TG, Curi R, de Bittencourt HPI Jr (2006) Low expression of MRP1/GS-X pump ATPase in lymphocytes of Walker 256 tumour-bearing rats is associated with cyclopentenone prostaglandin accumulation and cancer immunodeficiency. Cell Biochem Funct 24:23–39CrossRefPubMedGoogle Scholar
  16. 16.
    Krause M, Bock PM, Takahashi HK, de Bittencourt HPI Jr, Newsholme P (2015) The regulatory roles of NADPH oxidase, intra- and extra-cellular HSP70 in pancreatic islet function, dysfunction and diabetes. Clin Sci 128:789–803CrossRefPubMedGoogle Scholar
  17. 17.
    Krause M, de Bittencourt HPI Jr (2008) Type 1 diabetes: can exercise impair the autoimmune event? The L-arginine/glutamine coupling hypothesis. Cell Biochem Funct 26:406–433CrossRefGoogle Scholar
  18. 18.
    Krause M, Heck TG, Bittencourt A, Scomazzon SP, Newsholme P, Curi R, de Bittencourt HPI Jr (2015) The chaperone balance hypothesis: the importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Mediat Inflamm 2015:249205CrossRefGoogle Scholar
  19. 19.
    Lee MO (1929) The Function of the Air Sacs in Holopneustic Insects. Science 69:334–335CrossRefPubMedGoogle Scholar
  20. 20.
    Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S (2013) Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicol Pathol 41:361–373CrossRefPubMedGoogle Scholar
  21. 21.
    Ludwig MS, Minguetti-Camara VC, Heck TG, Scomazzon SP, Nunes PR, Bazotte RB, de Bittencourt HPI Jr (2014) Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF-alpha. Mol Cell Biochem 397:97–107CrossRefPubMedGoogle Scholar
  22. 22.
    Maatz LF, Wood GJ, Rivero DH & Saldiva PH et al (2009) Tracheal instillation of urban PM(2.5) suspension promotes acute cardiac polarization changes in rats. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas/Sociedade Brasileira de Biofisica 42:207–213Google Scholar
  23. 23.
    Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry/FEBS 47:469–474CrossRefGoogle Scholar
  24. 24.
    Medeiros N Jr, Rivero DH, Kasahara DI, Saiki M, Godleski JJ, Koutrakis P, Capelozzi VL, Saldiva PH, Antonangelo L (2004) Acute pulmonary and hematological effects of two types of particle surrogates are influenced by their elemental composition. Environ Res 95:62–70CrossRefPubMedGoogle Scholar
  25. 25.
    Mendez R, Zheng Z, Fan Z, Rajagopalan S, Sun Q, Zhang K (2013) Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue. Am J Transl Res 5:224–234PubMedPubMedCentralGoogle Scholar
  26. 26.
    Miller MR, Shaw CA, Langrish JP (2012) From particles to patients: oxidative stress and the cardiovascular effects of air pollution. Futur Cardiol 8:577–602CrossRefGoogle Scholar
  27. 27.
    Newsholme P, de Bittencourt HPI Jr (2014) The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease. Current opinion in clinical nutrition and metabolic care 17:295–305CrossRefPubMedGoogle Scholar
  28. 28.
    Pearson JF, Bachireddy C, Shyamprasad S, Goldfine AB & Brownstein JS (2010) Association between fine particulate matter and diabetes prevalence in the U.S..Diabetes care 33:2196–2201Google Scholar
  29. 29.
    Probst-Hensch NM (2010) Chronic age-related diseases share risk factors: do they share pathophysiological mechanisms and why does that matter? Swiss Med Wkly 140:w13072PubMedGoogle Scholar
  30. 30.
    Rajagopalan S, Brook RD (2012) Air pollution and type 2 diabetes: mechanistic insights. Diabetes 61:3037–3045CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Rodrigues-Krause J, Krause M, O'Hagan C, De Vito G, Boreham C, Murphy C, Newsholme P, Colleran G (2012) Divergence of intracellular and extracellular HSP72 in type 2 diabetes: does fat matter? Cell Stress Chaperones 17:293–302CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Schuster DP (2010) Obesity and the development of type 2 diabetes: the effects of fatty tissue inflammation. Diabetes, metabolic syndrome and obesity : targets and therapy 3:253–262CrossRefGoogle Scholar
  33. 33.
    Sone H, Kagawa Y (2005) Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia 48:58–67CrossRefPubMedGoogle Scholar
  34. 34.
    Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, Cai Y, Ostrowski MC, Lu B, Parthasarathy S et al (2009) Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 119:538–546CrossRefPubMedGoogle Scholar
  35. 35.
    Van Eeden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T, Qui D, Vincent R, Hogg JC (2001) Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med 164:826–830CrossRefPubMedGoogle Scholar
  36. 36.
    Walsh RC, Koukoulas I, Garnham A, Moseley PL, Hargreaves M, Febbraio MA (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 6:386–393CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    WHO (1998) Carbohydrates in human nutrition. Report of a Joint FAO/WHO Expert Consultation FAO food and nutrition paper 66:1–140Google Scholar
  38. 38.
    Winzell MS, Ahren B (2004) The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53(Suppl 3):S215–S219CrossRefPubMedGoogle Scholar
  39. 39.
    Xu X, Yavar Z, Verdin M, Ying Z, Mihai G, Kampfrath T, Wang A, Zhong M, Lippmann M, Chen LC et al (2010) Effect of early particulate air pollution exposure on obesity in mice: role of p47phox. Arterioscler Thromb Vasc Biol 30:2518–2527CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Yan YH, Chou CC, Lee CT, Liu JY, Cheng TJ (2011) Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation. Inhal Toxicol 23:507–519CrossRefPubMedGoogle Scholar

Copyright information

© University of Navarra 2016

Authors and Affiliations

  • Pauline Brendler Goettems-Fiorin
    • 1
    • 2
    • 3
  • Bethânia Salamoni Grochanke
    • 1
    • 2
    • 3
  • Fernanda Giesel Baldissera
    • 1
    • 2
    • 3
  • Analu Bender dos Santos
    • 1
    • 5
  • Paulo Ivo Homem de BittencourtJr
    • 4
  • Mirna Stela Ludwig
    • 1
    • 5
  • Claudia Ramos Rhoden
    • 2
  • Thiago Gomes Heck
    • 1
    • 5
    Email author
  1. 1.Research Group in Physiology, Department of Life SciencesRegional University of Northwestern Rio Grande do Sul State (UNIJUI)IjuíBrazil
  2. 2.Laboratory of Oxidative Stress and Air Pollution, Postgraduate Program in Health SciencesFederal University of Health Sciences of Porto Alegre (UFCSPA)Porto AlegreBrazil
  3. 3.Postgraduate Program in Health Sciences (PPGCS-UFCSPA)Porto AlegreBrazil
  4. 4.Laboratory of Cellular Physiology (FisCel), Department of PhysiologyFederal University of Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  5. 5.Postgraduate Program in Integral Attention to Health (PPGAIS-UNIJUI/UNICRUZ)IjuíBrazil

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