Title: Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue.
Authors: Xu, Xiaohua; Liu, Cuiqing; Xu, Zhaobin; Tzan, Kevin; Zhong, Mianhua; Wang, Aixia; Lippmann, Morton; Chen, Lung-Chi; Rajagopalan, Sanjay; Sun, Qinghua
Published In Toxicol Sci, (2011 Nov)
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.
PubMed ID: 21873646
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