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

Zhaobin Xu,Morton Lippmann,Aixia Wang,Ryan P Lewandowski,Qinghua Sun,Jack R Harkema,Yifeng Yang,Xiaohua Xu,Sanjay Rajagopalan,James G Wagner,Lori A Bramble,Ian P Hotchkiss,Mianhua Zhong,Lung-Chi Chen

doi:10.1186/1743-8977-8-20

Abstract

BackgroundPrior 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.MethodsMale 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.ResultsExposure 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.ConclusionsPM2.5 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.

Highlights

Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes
Superoxide (O2-) generation In order to test whether exposure to PM2.5 results in superoxide production in brown adipose tissue (BAT), we performed dihydroethidium (DHE) staining on interscapular BAT (iBAT) depots
O2- that was accumulated in the iBAT of the mice exposed to PM2.5 was approximately 80% increase from filtered air (FA)-exposed controls

Summary

Introduction

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. 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. There are at least two distinct types of adipose cells, white and brown adipocytes, with opposing effects on energy balance and body weight regulation. Brown adipose gene expression could be stimulated when mice are maintained at thermoneutrality and under conditions of cold acclimation [7,8]

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