title: Effect of early particulate air pollution exposure on obesity in mice: role of p47phox.
abstract: OBJECTIVE
  To evaluate the role of early-life exposure to airborne fine particulate matter (diameter, <2.5 μm [PM(2.5)]) pollution on metabolic parameters, inflammation, and adiposity; and to investigate the involvement of oxidative stress pathways in the development of metabolic abnormalities.
  
  
  RESULTS
  PM(2.5) inhalation exposure (6 h/d, 5 d/wk) was performed in C57BL/6 mice (wild type) and mice deficient in the cytosolic subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47(phox) (p47(phox-/-)) beginning at the age of 3 weeks for a duration of 10 weeks. Both groups were simultaneously fed a normal diet or a high-fat diet for 10 weeks. PM(2.5)-exposed C57BL/6 mice fed a normal diet exhibited metabolic abnormalities after exposure to PM(2.5) or FA for 10 weeks. Consistent with insulin resistance, these abnormalities included enlarged subcutaneous and visceral fat contents, increased macrophage infiltration in visceral adipose tissue, and vascular dysfunction. Ex vivo-labeled and infused monocytes demonstrated increased adherence in the microcirculation of normal diet- or high-fat diet-fed PM(2.5)-exposed mice. p47(phox-/-) mice exhibited an improvement in parameters of insulin resistance, vascular function, and visceral inflammation in response to PM(2.5).
  
  
  CONCLUSIONS
  Early-life exposure to high levels of PM(2.5) is a risk factor for subsequent development of insulin resistance, adiposity, and inflammation. Reactive oxygen species generation by NADPH oxidase appears to mediate this risk.
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus 43210, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Zubin
authors.initials: Z
authors.lastname: Yavar
authors.forename: Matt
authors.initials: M
authors.lastname: Verdin
authors.forename: Zhekang
authors.initials: Z
authors.lastname: Ying
authors.forename: Georgeta
authors.initials: G
authors.lastname: Mihai
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampfrath
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.forename: Mianhua
authors.initials: M
authors.lastname: Zhong
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: D050154:Adiposity; D000367:Age Factors; D000375:Aging; D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004041:Dietary Fats; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D019570:Inhalation Exposure; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000201:enzymology* / Q000503:physiopathology; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D018836:Inflammation Mediators; D007328:Insulin; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1