Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

Part Fibre Toxicol. 2011 Jul 11:8:20. doi: 10.1186/1743-8977-8-20.

Abstract

Background: Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model.

Methods: Male ApoE knockout (ApoE-/-) mice inhaled concentrated fine ambient PM (PM < 2.5 μm in aerodynamic diameter; PM2.5) or filtered air (FA) for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli.

Results: Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT) and brown adipose tissues (BAT), while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated.

Conclusions: PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / drug effects*
  • Adipose Tissue, Brown / physiology*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects*
  • Adipose Tissue, White / physiology*
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Energy Metabolism / drug effects
  • Gene Expression / drug effects*
  • Humans
  • Ion Channels / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism
  • Oxidative Stress / drug effects*
  • Particle Size
  • Particulate Matter / metabolism
  • Particulate Matter / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Uncoupling Protein 1

Substances

  • Apolipoproteins E
  • Ion Channels
  • Mitochondrial Proteins
  • Particulate Matter
  • Reactive Oxygen Species
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1