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

Publisher: National Institute of Environmental Health Sciences Country of Publication: United States NLM ID: 0330411 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-9924 (Electronic) Linking ISSN: 00916765 NLM ISO Abbreviation: Environ Health Perspect Subsets: MEDLINE

Original Publication: Research Triangle Park, N. C. National Institute of Environmental Health Sciences.

Insulin Resistance*; Air Pollutants/*toxicity ; Particulate Matter/*toxicity; Animals ; Antioxidants/pharmacology ; Cyclic N-Oxides/pharmacology ; Diet, High-Fat/adverse effects ; Free Radical Scavengers/metabolism ; Lung/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Particle Size ; Spin Labels ; Superoxide Dismutase/metabolism

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. 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.
Competing Interests: The authors declare they have no actual or potential competing financial interests.

Comment in: Environ Health Perspect. 2016 Dec 1;124(12 ):A236. (PMID: 27905277)

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P20 GM103492 United States GM NIGMS NIH HHS; R01 ES019217 United States ES NIEHS NIH HHS; R01 HL055477 United States HL NHLBI NIH HHS

0 (Air Pollutants)
0 (Antioxidants)
0 (Cyclic N-Oxides)
0 (Free Radical Scavengers)
0 (Particulate Matter)
0 (Spin Labels)
EC 1.15.1.1 (Superoxide Dismutase)
U78ZX2F65X (tempol)

Date Created: 20160430 Date Completed: 20170901 Latest Revision: 20220410

20221213

PMC5132639

10.1289/EHP212

27128347