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PMID: 21873646 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Toxicological sciences : an official journal of the Society of Toxicology ·Vol. 124 ·No. 1 ·2011-11-00 ·Pages 88-98

Xu X, Liu C, Xu Z, Tzan K, Zhong M, Wang A, Lippmann M, Chen LC, Rajagopalan S, Sun Q

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.

MeSH Terms
Adiponectin/blood Adipose Tissue/drug effects,metabolism,ultrastructure Air Pollutants/toxicity Animals Biomarkers/blood Blotting, Western Diabetes Mellitus, Type 2/blood,etiology,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,genetics,ultrastructure Mitochondrial Proteins/genetics Mitochondrial Size/drug effects NF-E2-Related Factor 2/genetics Organ Specificity Oxidative Stress/drug effects,genetics Particle Size Particulate Matter/toxicity Real-Time Polymerase Chain Reaction Risk Factors Time Factors Uncoupling Protein 1
Chemicals
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
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Xu Xiaohua
Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
Liu Cuiqing
Xu Zhaobin
Tzan Kevin
Zhong Mianhua
Wang Aixia
Lippmann Morton
Chen Lung-Chi
Rajagopalan Sanjay
Sun Qinghua
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Article Info
Journal
Toxicological sciences : an official journal of the Society of Toxicology
Abbr.
Toxicol Sci
ISSN
1096-0929
DOI
10.1093/toxsci/kfr211
Published
2011-11-00
Epub
2011-00-27
Pages
88-98
Language
English
Region
United States
NLM ID
9805461
PMCID
PMC3196653
Subset
IM
Grants
NIEHS NIH HHS · ES017412 · United States
NIEHS NIH HHS · ES015146 · United States
NIEHS NIH HHS · ES00260 · United States
NIEHS NIH HHS · ES016588 · United States
NIEHS NIH HHS · R01 ES018900 · United States
NIEHS NIH HHS · ES018900 · United States
External Links
PubMed source DOI: 10.1093/toxsci/kfr211 PMC Full Text View journal details
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