Background: 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.
Objectives: We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress.
Methods: 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.
Results: 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.
Conclusions: 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.
Diabetes and Obesity Center, Institute of Molecular Cardiology, School of Medicine, University of Louisville, Louisville, Kentucky, USA
Recommended Citation:
Petra Haberzettl,Timothy E. O’Toole,Aruni Bhatnagar,et al. Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress[J]. Environmental Health Perspectives,2016-01-01,Volume 124(Issue 12):1830