title: Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue.
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.
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Liu
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Xu
authors.forename: Kevin
authors.initials: K
authors.lastname: Tzan
authors.forename: Mianhua
authors.initials: M
authors.lastname: Zhong
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.forename: Morton
authors.initials: M
authors.lastname: Lippmann
authors.forename: Lung-Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D019570:Inhalation Exposure / Q000009:adverse effects*; D007333:Insulin Resistance; D007473:Ion Channels / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics; D053142:Mitochondrial Size / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D000071256:Uncoupling Protein 1
chemical_list: D052242:Adiponectin; D000393:Air Pollutants; D015415:Biomarkers; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D052638:Particulate Matter; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1