Abstract
BackgroundIt has been well recognized that toxicity of fine ambient air particulate matter (PM2.5) may depend on its chemical constituents, including components such as soluble metals that may theoretically exert distinctive effects. We have recently demonstrated an important effect of PM2.5 on metabolic function. Since transition metals, such as nickel (Ni), represent an important component of exposure in certain environments, and may significantly influence the toxicity of inhalational exposure, we investigated the effects of Ni as a variable component of ambient PM2.5 exposure.MethodsMale ApoE knockout mice were exposed to filtered air (FA), fine-sized nickel sulfate particles alone (Ni) at 0.44 μg/m3, concentrated ambient air PM2.5 (CAPs) at a mean of 70 μg/m3, or CAPs+Ni in Tuxedo, NY, 6 hours/day, 5 days/week, for 3 months.ResultsExposure to Ni, irrespective of co-exposure to CAPs, resulted in body weight gain, while exposure to CAPs+Ni significantly enhanced fasting glucose and worsened insulin resistance measures (HOMA-IR), when compared with exposure to CAPs alone. CAPs+Ni exposure induced a significant decrease in phosphorylation of AMP-activated protein kinase (AMPK) α. Exposure to Ni or CAPs+Ni significantly induced microcirculatory dysfunction and increased monocytic cell infiltration into lung and adipose, and decreased uncoupling protein 1 expression at gene and protein levels and several brown adipocyte-specific genes in adipose tissue.ConclusionsNi exposure has effects on metabolic and inflammatory parameters that are comparable to that of CAPs. Additionally, Ni synergistically exacerbates CAPs-induced adverse effects on some of, but not all of, these parameters, that may be mediated via the AMPK signaling pathway. These findings have important implications for inhaled transition metal toxicity that may exert synergistic effects with other PM2.5 components.
Highlights
It has been well recognized that toxicity of fine ambient air particulate matter (PM2.5) may depend on its chemical constituents, including components such as soluble metals that may theoretically exert distinctive effects
Laden et al [8] demonstrated that Ni was positively associated with daily deaths through studies in six U.S Cities, and Lippmann et al [1] showed significant associations of Ni with daily deaths in 60 U.S, cities, as well as changes in heart rate variability (HRV) in mice that were highly correlated with Ni levels in the air that they inhaled
We have previously demonstrated that PM2.5 air pollution potentiates multiple facets of metabolic function including inflammation, adiposity, and brown adipose dysfunction, and that it is a factor that contributes to the development of insulin resistance (IR) through these various pathways [9,10,11,12,13,14]
Summary
It has been well recognized that toxicity of fine ambient air particulate matter (PM2.5) may depend on its chemical constituents, including components such as soluble metals that may theoretically exert distinctive effects. We have recently demonstrated an important effect of PM2.5 on metabolic function Since transition metals, such as nickel (Ni), represent an important component of exposure in certain environments, and may significantly influence the toxicity of inhalational exposure, we investigated the effects of Ni as a variable component of ambient PM2.5 exposure. The components of PM2.5 responsible for these effects continue to remain unclear It has, been well recognized that toxicity of the PM2.5 depends, at least in part, on the specific chemicals that are present, and that metals are often implicated as causative agents. Back trajectory analyses for the highest Ni concentrations led to the vicinity of the largest nickel smelter in North America at Sudbury, Ontario
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