Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

• DOI: 10.1038/srep23963
• Publication Date: 2016-04-01T09:08:53Z
• Authors: Nanyang Yu; Si Wei; Meiying Li; Jingping Yang; Kan Li; Ling Jin; Yuwei Xie; John P. Giesy; Xiaowei Zhang; Hongxia Yu
• Keywords: Brain Chemistry; Male; 0301 basic medicine; Fluorocarbons; Mice, Inbred BALB C; Neurotransmitter Agents; Body Weight; Lipid Metabolism; 01 natural sciences; Article; High-Throughput Screening Assays; 3. Good health; Mice; 03 medical and health sciences; Liver; Organ Specificity; Animals; Metabolomics; Environmental Pollutants; Caprylates; 0105 earth and related environmental sciences

AbstractPerfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.