Metabolomic Analysis of the Effects of Chronic Arsenic Exposure in a Mouse Model of Diet-Induced Fatty Liver Disease

Abstract

Arsenic is a widely-distributed environmental component that is associated with a variety of cancer and non-cancer adverse health effects. Additional lifestyle factors, such as diet, contribute to the manifestation of disease. Recently, arsenic was found to increase inflammation and liver injury in a dietary model of fatty liver disease. The purpose of the present study was to investigate potential mechanisms of this diet-environment interaction via a high throughput metabolomics approach. GC×GC-TOF MS was used to identify metabolites that were significantly increased or decreased in the livers of mice fed a Western diet (a diet high in fat and cholesterol) and co-exposed to arsenic-contaminated drinking water. The results showed that there are distinct hepatic metabolomic profiles associated with eating a high fat diet, drinking arsenic-contaminated water, and the combination of the two. Among the metabolites that were decreased when arsenic exposure was combined with a high fat diet were short-chain and medium-chain fatty acid metabolites and the anti-inflammatory amino acid, glycine. These results are consistent with the observed increase in inflammation and cell death in the livers of these mice, and they point to potentially novel mechanisms by which these metabolic pathways could be altered by arsenic in the context of diet-induced fatty liver disease.

Chronic low level arsenic exposure evokes inflammatory responses and DNA damage

“…Arsenic exposure increased susceptibility of C57BL/6 mice to respiratory infections and inflammation (Ramsey et al, 2013). Arsenic was also found to be associated with inflammation induced alteration of metabolic pathway in fatty livers of C57BL/6J mice (Shi et al, 2014). Evidence suggests that As has inductive effect on CD14 expression of human macrophages (Lemarie et al, 2006).…”

Health Effects of Metals in Particulate Matter

“…This is done through the modulation of transcription factors like NF-kB, AP-1 and p53 that promotes liver tumors. Likewise, Arsenic causes liver lipoperoxidation producing large amounts of ROS [152]. Also a decrease in the levels of the superoxide dismutase enzymes (SOD), catalase (CAT) and glutathione peroxidase has been reported [153].…”

Normal–Gamma–Bernoulli peak detection for analysis of comprehensive two-dimensional gas chromatography mass spectrometry data

“…Compared with other analytical platforms, GC×GC-MS can significantly increase the separation power by 3–10 folds, depending on the sample complexity and instrument operation (Winnike et al, 2015). Therefore, GC×GC-MS has been increasingly used in metabolomics for biomarker discovery (Phillips et al, 2013; Ralsoton-Hooper et al, 2008; Schmidt et al, 2013; Shi et al, 2014). …”