Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity

Abstract

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) 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-α/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. Conclusion— 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.