Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, Cai Y, Ostrowski MC, Lu B, Parthasarathy S, Brook RD, Moffatt-Bruce SD, Chen LC, Rajagopalan S.

Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity

BACKGROUND: There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (<2.5 mum; PM(2.5)) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity. METHODS AND RESULTS: Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM(2.5) or filtered air (n=14 per group) for 24 weeks. PM(2.5)-exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM(2.5) exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM(2.5) increased adipose tissue macrophages (F4/80(+) cells) in visceral fat expressing higher levels of tumor necrosis factor-alpha/interleukin-6 and lower interleukin-10/N-acetyl-galactosamine specific lectin 1. To test the impact of PM(2.5) in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c-fms, c-fms(YFP)) diabetic over 10 weeks and then exposed these mice to PM(2.5) or saline intratracheally. PM(2.5) induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation. CONCLUSIONS: PM(2.5) exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus.