Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue

Toxicol Sci. 2011 Nov;124(1):88-98. doi: 10.1093/toxsci/kfr211. Epub 2011 Aug 27.

Abstract

We have previously shown that chronic exposure to ambient fine particulate matter (less than 2.5 μm in aerodynamic diameter, PM₂.₅) pollution in conjunction with high-fat diet induces insulin resistance through alterations in inflammatory pathways. In this study, we evaluated the effects of PM₂.₅ exposure over a substantive duration of a rodent's lifespan and focused on the impact of long-term exposure on adipose structure and function. C57BL/6 mice were exposed to PM₂.₅ or filtered air (FA) (6 h/day, 5 days/week) for duration of 10 months in Columbus, OH. At the end of the exposure, PM₂.₅-exposed mice demonstrated insulin resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed group. Although there were no significant differences in circulating cytokines between PM₂.₅- and FA-exposed groups, circulating adiponectin and leptin were significantly decreased in PM₂.₅-exposed group. PM₂.₅ exposure also led to inflammatory response and oxidative stress as evidenced by increase of Nrf2-regulated antioxidant genes. Additionally, PM₂.₅ exposure decreased mitochondrial count in visceral adipose and mitochondrial size in interscapular adipose depots, which were associated with reduction of uncoupling protein 1 (UCP1) expression and downregulation of brown adipocyte-specific gene profiles. These findings suggest that long-term ambient PM₂.₅ exposure induces impaired glucose tolerance, IR, inflammation, and mitochondrial alteration, and thus, it is a risk factor for the development of type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / ultrastructure
  • Air Pollutants / toxicity*
  • Animals
  • Biomarkers / blood
  • Blotting, Western
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • Inhalation Exposure / adverse effects*
  • Insulin Resistance*
  • Ion Channels / genetics
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Size / drug effects
  • NF-E2-Related Factor 2 / genetics
  • Organ Specificity
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Particle Size
  • Particulate Matter / toxicity*
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Time Factors
  • Uncoupling Protein 1

Substances

  • Adiponectin
  • Air Pollutants
  • Biomarkers
  • Ion Channels
  • Leptin
  • Mitochondrial Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Particulate Matter
  • Ucp1 protein, mouse
  • Uncoupling Protein 1