Effect of co-exposure to nickel and particulate matter on insulin resistance and mitochondrial dysfunction in a mouse model

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.

Particulate matter components, sources, and health: Systematic approaches to testing effects

“…This approach was used by Xu et al (2012) in which mice were exposed to nickel sulfate, CAPs, or a combination of nickel sulfate and CAPs; they showed that nickel and CAPs had synergistic effects on some of the metabolic and inflammatory endpoints measured; Huang et al (2012) observed synergistic effects of NO 2 and fine CAPs on cardiovascular responses in healthy young volunteers.…”

In Vivo Exposures to Particulate Matter Collected from Saudi Arabia or Nickel Chloride Display Similar Dysregulation of Metabolic Syndrome Genes

“…Niu et al (2013) noted that metallic components of PM may be responsible for the cardiovascular disorders produced by PM exposures. Nickel has long been reported from epidemiological and molecular studies to promote cardiovascular disease (Bell et al, 2014; Ying et al, 2013), respiratory cancers (Grimsrud and Peto, 2006), insulin resistance (Xu et al, 2012) and mortality (Laden et al, 2000). Hsu and Lippmann (2007) previously found that the levels of Ni in concentrated ambient particulate (CAP) matter PM 2.5 were strongly correlated to acute changes in heart rates and their variability.…”

Mitochondrial toxicity of tobacco smoke and air pollution

“…Mass-spectrometry analysis has already demonstrated the presence of aldehydes, free radicals, and metals which are known mitochondrial toxicants and may act through similar disease mechanisms as those triggered by cigarette smoke exposure 312–317 . Other tobacco products including hookahs, little cigars, and cigarillos combust tobacco leaves in a fashion very similar to traditional cigarettes and therefore, likely contain the same toxicants and carcinogens found in tobacco cigarette smoke.…”