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

J Physiol Biochem. 2016 Dec;72(4):643-656. doi: 10.1007/s13105-016-0503-7. Epub 2016 Jun 29.


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; Blood glucose; Glycemic control; HSP70; Heat shock protein; Particulate matter.

MeSH terms

  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology
  • Administration, Intranasal
  • Animals
  • Biomarkers / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Diet, High-Fat / adverse effects
  • Gene Expression Regulation
  • Glucose Intolerance / chemically induced
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / pathology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP72 Heat-Shock Proteins / genetics
  • HSP72 Heat-Shock Proteins / metabolism*
  • Insulin Resistance
  • Male
  • Mice
  • Obesity / chemically induced
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Oxidative Stress / drug effects
  • Particulate Matter / toxicity*
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Weight Gain / drug effects


  • Biomarkers
  • HSP70 Heat-Shock Proteins
  • HSP72 Heat-Shock Proteins
  • Particulate Matter
  • Catalase
  • Superoxide Dismutase