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

Xu Zhaobin, Xu Xiaohua, Zhong Mianhua, Hotchkiss, Lewandowski, Wagner, Bramble, Yang Yifeng, Wang Aixia, Harkema, Lippmann Morton, Rajagopalan Sanjay, Chen Lung-Chi, Sun Qinghua

Description

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; PM 2.5 ) 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 PM 2.5 exposure in different adipose depots of ApoE -/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM 2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM 2.5 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, PM 2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM 2.5 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 PM 2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

Sujets

• Air pollution
• Mitocondria
• Adipose tissue
• Oxidative stress
• Inflammation

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Xuet al.Particle and Fibre Toxicology2011,8:20 http://www.particleandfibretoxicology.com/content/8/1/20

R E S E A R C H

Open Access

Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues 1,2 2 3 4 4 4 Zhaobin Xu , Xiaohua Xu , Mianhua Zhong , Ian P Hotchkiss , Ryan P Lewandowski , James G Wagner , 4 1 5 4 3 5,6 Lori A Bramble , Yifeng Yang , Aixia Wang , Jack R Harkema , Morton Lippmann , Sanjay Rajagopalan , 3* 2,5,6* LungChi Chen and Qinghua Sun

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 < 2.5μm in aerodynamic diameter; PM 2.5 ) 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 PM 2.5 mice to understandexposure in different adipose depots of ApoE responses to chronic inhalational stimuli. Results:Exposure to PM 2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM decreased expression of uncoupling protein 1 in brown adipose 2.5 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, PM 2.5 exposure downregulated brown adipocytespecific genes, while white adipocytespecific genes were differentially upregulated. Conclusions:PM 2.5 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 PM 2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction. Keywords:air pollution, mitochondria, adipose, oxidative stress, inflammation

* Correspondence: Lung[e-mail]; [e-mail] 2 Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, USA 3 The Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA Full list of author information is available at the end of the article

© 2011 Xu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.