Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis
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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.
KeywordsAdiposity Particulate matter Glycemic control Heat shock protein HSP70 Blood glucose
Epididymal white adipose tissue
Glucose tolerance test
The 70-kDa family of heat shock proteins
Extracellular 70-kDa heat shock proteins
Intracellular 70-kDa heat shock proteins
Incremental area under the curve
Nuclear factor-kappa B
Nutrient metabolism-related tissues
Fine particulate matter
Sodium dodecyl sulfate
Type 2 diabetes
Tosyl-l-lysine chloromethyl ketone hydrochloride
Toll-like receptor 2
Toll-like receptor 4
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.
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
The authors declare that they do not have competing financial interests.
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).
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