Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress

Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. We tested the hypothesis that PM2.5 exposure decreases...

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Bibliographic Details
Published in:Environmental health perspectives 2016-12, Vol.124 (12), p.1830-1839
Main Authors: Haberzettl, Petra, O'Toole, Timothy E, Bhatnagar, Aruni, Conklin, Daniel J
Format: Article
Language:English
Subjects:
Adipose tissue
Air Pollutants - toxicity
Air pollution
Animals
Antioxidants
Antioxidants - pharmacology
Asthma
Body fat
Cardiovascular diseases
Causes of
Cyclic N-Oxides - pharmacology
Cytokines
Diabetes
Diet
Diet, High-Fat - adverse effects
Disease
Exposure
Free Radical Scavengers - metabolism
Glucose
Health aspects
Inflammation
Influenza
Insulin Resistance
Kinases
Lung - drug effects
Lungs
Male
Metabolic disorders
Metabolism
Mice
Mice, Inbred C57BL
Nitric oxide
Obesity
Oxidative stress
Oxidative Stress - drug effects
Particle Size
Particulate matter
Particulate Matter - toxicity
Plasma
Risk factors
Rodents
Spin Labels
Studies
Superoxide Dismutase - metabolism
Variance analysis
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Summary:Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diets, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or to concentrated PM2.5 (CAP) for 9 or 30 days, and changes in systemic and organ-specific insulin sensitivity and inflammation were measured. In control diet-fed mice, exposure to CAP for 30 days decreased insulin-stimulated Akt phosphorylation in lung, heart, and aorta but not in skeletal muscle, adipose tissue, and liver and did not affect adiposity or systemic glucose tolerance. In HFD-fed mice, 30-day CAP exposure suppressed insulin-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation in skeletal muscle and increased adipose tissue inflammation and systemic glucose intolerance. In control diet-fed mice, a 9-day CAP exposure was sufficient to suppress insulin-stimulated Akt and eNOS phosphorylation and to decrease IκBα (inhibitor of the transcription factor NF-κB levels in the aorta. Treatment with the antioxidant TEMPOL or lung-specific overexpression of ecSOD prevented CAP-induced vascular insulin resistance and inflammation. Short-term exposure to PM2.5 induces vascular insulin resistance and inflammation triggered by a mechanism involving pulmonary oxidative stress. Suppression of vascular insulin signaling by PM2.5 may accelerate the progression to systemic insulin resistance, particularly in the context of diet-induced obesity. Citation: Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. 2016. Exposure to fine particulate air pollution causes vascular insulin resistance by inducing pulmonary oxidative stress. Environ Health Perspect 124:1830-1839; http://dx.doi.org/10.1289/EHP212.
ISSN:0091-6765
1552-9924
DOI:10.1289/EHP212