title: Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.
abstract: 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.
authors.affiliation: Diabetes and Obesity Center, Institute of Molecular Cardiology, School of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Haberzettl
authors.forename: Timothy E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D016166:Free Radical Scavengers / Q000378:metabolism; D007333:Insulin Resistance; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D052638:Particulate Matter; D013113:Spin Labels; D013482:Superoxide Dismutase; C001803:tempol