Date on Master's Thesis/Doctoral Dissertation

12-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Degree Program

Chemistry, PhD

Committee Chair

Zhang, Xiang

Committee Co-Chair (if applicable)

Nantz, Michael

Committee Member

Baldwin, Richard

Committee Member

Watson, Walter

Subject

Liver--Diseases--Diagnosis; Mass spectrometry; Biochemical markers

Abstract

Metabolomics has emerged as one of the latest of the "-omics" disciplines that can detect metabolite biomarkers in biological samples. The diverse characteristics of metabolites make the analytical platform challenging in metabolomics. Two bioanalytical platforms were developed in this study to investigate metabolite abundance changes under different biological conditions. We first developed a bioanalytical platform that coupled linear trap quadruple - Fourier transform ion cyclotron mass spectrometer (LTQ-FTICR MS) with direct infusion chip-based nano-electrospray ionization (DI-nESI) and applied it to study polychlorinated biphenyls (PCB) effects on non-alcoholic fatty liver disease (NAFLD). We also employed this platform in conjunction with in vivo metabolite deuterium labeling to study whether chronic alcohol exposure disturbs lipid homeostasis by analyzing triacylglycerol regulation alteration in adipose tissue and liver tissue. We further developed a comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) platform for metabolomic profiling and applied it to study the effects of arsenic exposure in a mouse model of diet-induced fatty liver disease, as well as the effects of Lactobacillus rhamnosus GG on alcoholic fatty liver disease (AFLD) in mice. The results of our metabolomics analyses agreed with the results of histological studies and provided molecular level information for further understanding the mechanisms of liver diseases.

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