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

Abstract

Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admissions, and diseases associated with metabolic syndrome, including diabetes mellitus, cardiovascular disease, and obesity. In a previous in vitro and in vivo study, data demonstrated that PM_10μm collected from Jeddah, Saudi Arabia (PM_SA), altered expression of genes involved in lipid and cholesterol metabolism, as well as many other genes associated with metabolic disorders. PM_SA contains a relatively high concentration of nickel (Ni), known to be linked to several metabolic disorders. In order to evaluate whether Ni and PM exposures induce similar gene expression profiles, mice were exposed to 100 μg/50 μl PM_SA (PM-100), 50 μg/50 μl nickel chloride (Ni-50), or 100 μg/50 μl nickel chloride (Ni-100) twice per week for 4 wk and hepatic gene expression changes were determined. Ultimately, 55 of the same genes were altered in all 3 exposures. However, where the two Ni groups differed markedly was in the regulation (up or down) of these genes. Ni-100 and PM-100 groups displayed similar regulations, whereby 104 of the 107 genes were similarly modulated. Many of the 107 genes are involved in metabolic syndrome and include ALDH4A1, BCO2, CYP1A, CYP2U, TOP2A. In addition, the top affected pathways, such as fatty acid α-oxidation, and lipid and carbohydrate metabolism, are involved in metabolic diseases. Most notably, the top diseased outcome affected by these changes in gene expression was cardiovascular disease. Given these data, it appears that Ni and PM_SA exposures display similar gene expression profiles, modulating the expression of genes involved in metabolic disorders.

Additional information

Funding

The authors thank New York University (NYU) and King Abdulaziz University (KAU) for technical and financial support. This work was supported by the National Institutes of Health (NIH), grants ES010344, ES014454, ES000260, ES022935, ES023174, and ES005512 and by King Abdulaziz University (KAU), Jeddah, grant 4/00/00/252.