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Goal: The proposed work aims to examine the metabolic events elicited by consumption of heated highly-unsaturated vegetable oils and to identify small-molecule biomarkers associated with the toxicities using metabolomic approaches.<P> Objective 1: To identify endogenous small-molecule biomarkers of heated soybean oil-induced toxicities through long-term feeding and metabolomic analysis of changes in urine, serum and tissue samples, and to establish the correlation between biomarkers and toxicological parameters<P> Objective 2: To identify fractions of heated soybean oil that are responsible for the toxicities and metabolic events associated with identified biomarkers, and to investigate the metabolic fates of hydroxyalkenals. <P>Output: The successful completion of this project will not only provide novel information on the pathogenesis of LOPs-related toxicities, but also set the knowledge base for translating the identified biomarkers into clinical practice and developing new prevention strategies against the risks from the exposure of heated unsaturated oils.
Non-Technical Summary: In recent years, consumption of food and feed containing heated and processed dietary fats such as heated vegetable oils has markedly increased in humans and animals. Under thermal stress, highly unsaturated oils are prone to be oxidized and degraded to various reactive lipid oxidation products (LOPs). Since the interaction between LOPs and biomolecules (protein, DNA and lipids) can potentially disrupt normal biochemical and signaling pathways regulating energy metabolism, inflammation, cell death and proliferation, the causative roles of consuming food prepared using highly unsaturated oils have been implicated in the pathogenesis of chronic diseases, including atherosclerosis, cancer and Alzheimer's disease, even though the underlying mechanisms are still poorly understood. Our current proposal intends to focus our efforts on understanding the influence of heated oils on the metabolic system and identifying biomarkers that can function as the indicators of prior exposures of heated vegetable oils and related toxic events, in the biological samples obtained from exposed humans and animals. <P> Approach: In this study, we will combine advanced mass spectrometry (both LC-MS and GC-MS) with multivariate analysis and animal models to identify and characterize endogenous metabolites that can function as the biomarkers of adverse effects induced by heated soybean oils (HSO). In order to distinguish the endogenous metabolites related to the toxicities from the exogenous metabolites introduced by HSO exposure, the bolus dosing experiment will be conducted to define the chromatographic and spectral properties of LOPs and their metabolites, while the feeding experiment will be performed to identify the biomarkers through analyzing the kinetic profile of metabolome during the initiation and progression of HSO-induced toxicities. Identified biomarkers will be characterized by examining their correlations with general toxicological parameters, and the mechanisms of HSO-induced toxicities will be implied by the biological functions of identified biomarkers. In addition, fractions of HSO that are responsible for the toxicities and metabolic events associated with identified biomarkers will be determined, and metabolic fates of hydroxyalkenals will also be investigated. We expect the application of mass spectrometry (MS)-based metabolomics in this project will provide us a good opportunity to observe previously unnoticed effects of heated oils and obtain novel information for further mechanistic investigation.