title: 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 point to potentially novel mechanisms by which these metabolic pathways could be altered by arsenic in the context of diet-induced fatty liver disease.
authors: Department of Chemistry, University of Louisville, Louisville, KY 40292.
authors: Xue
authors: X
authors: Shi
authors: Department of Chemistry, University of Louisville, Louisville, KY 40292.
authors: Xiaoli
authors: X
authors: Wei
authors: Department of Chemistry, University of Louisville, Louisville, KY 40292.
authors: Imhoi
authors: I
authors: Koo
authors: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292.|Department of Alcohol Research Center, University of Louisville, Louisville, KY 40292.
authors: Robin H
authors: RH
authors: Schmidt
authors: Department of Chemistry, University of Louisville, Louisville, KY 40292.
authors: Xinmin
authors: X
authors: Yin
authors: Biostatistics Core, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201.
authors: Seong Ho
authors: SH
authors: Kim
authors: Department of Medicine, University of Louisville, Louisville, KY 40292.
authors: Andrew
authors: A
authors: Vaughn
authors: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292.|Department of Alcohol Research Center, University of Louisville, Louisville, KY 40292.|Department of Medicine, University of Louisville, Louisville, KY 40292.|Department of Robley Rex VAMC, Louisville, KY 40292.
authors: Craig J
authors: CJ
authors: McClain
authors: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292.|Department of Alcohol Research Center, University of Louisville, Louisville, KY 40292.
authors: Gavin E
authors: GE
authors: Arteel
authors: Department of Chemistry, University of Louisville, Louisville, KY 40292.
authors: Xiang
authors: X
authors: Zhang
authors: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292.|Department of Alcohol Research Center, University of Louisville, Louisville, KY 40292.|Department of Medicine, University of Louisville, Louisville, KY 40292.
authors: Walter H
authors: WH
authors: Watson
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002849:Chromatography, Gas; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001151:Arsenic