Novel metabolites of acetate and lipidic aldehydes in mice and pigs through metabolomics-based identification and characterization.

Abstract

This dissertation explores the identification and characterization of novel metabolites of acetate and lipidic aldehydes in animal models. Advanced metabolomics techniques are utilized to elucidate the metabolic pathways and health impacts of these compounds, which are significant due to their presence in common foods and endogenous production.Acetate, a vital metabolite involved in numerous metabolic processes, serves as a precursor for acetyl-CoA, essential for energy production and biosynthesis. This research validates urinary N-acetyltaurine (NAT) as a potential biomarker for hyperacetatemia, providing a non-invasive method to monitor circulating acetate levels. Lipidic aldehydes, formed during the thermal oxidation of lipids and fats, are highly reactive and have been shown to substantially influence cellular metabolism and the health of humans and animals. This study investigates the disposition of aldehydes in the gastrointestinal tract of pigs fed oxidized oils, assessing their biotransformation and influence on nutrient digestion. The findings revealed the importance and potential contribution of de-novo aldehyde formation within the gastrointestinal tract to host health. Additionally, urinary markers responsive to lipidic aldehyde intake were characterized and identified in a mouse model. The results demonstrated the potential for new methods of assessing dietary aldehyde intake. Additional lipidomic analysis of the oils highlights the broader impacts of other lipid oxidation products in thermally oxidized oils on the host metabolism and health. All these insights enhance the understanding of acetate and lipidic aldehyde metabolism, offering new biomarkers for monitoring their dietary intake and metabolic states. Meanwhile, the findings call for further investigation into the comprehensive profiling of lipid oxidation products in oils, and their respective disposition and metabolic consequences.