Omics: Discovery of novel oxylipins and the proteins that regulate them

Oxylipins are signaling lipids that regulate inflammation, energy expenditure, and pain perception. Despite their importance, the mechanisms that regulate these oxylipins and the breadth of the oxylipins themselves remains under-explored. 

We identified a novel 4-hydroxylation of acylcarnitines that is associate with cardiovascular disease, and developed a targeted method to distinguish the position of the 4-hydroxylation in acylcarnitines and fatty acids from the 3- and 9-hydroxylations that are most prevalent. In collaboration with the Pagliarini lab we worked to identify the enzymes responsible for the catabolism of these 4-hydroxylated fatty acids processing these from complex matrixes spanning cell culture, murine studies, and plasma.

Many oxylipins are in low abundance, but through curation of a targeted library with the Agilent 6495D Triple Quadrupole LC/MS system, we can detect 154 distinct species. Through employment of this oxylipin library, which includes the 4-hydroxylated fatty acids and acylcarnitines, allowed us to determine how these lipids are regulated by diet, physiological stress, and disease state. Future work will aim to understand the function of these 4-hydroxylated acylcarnitines and determine how they are dysregulated in cardiovascular disease.

Presenter: Judi Simcox (University of Wisconsin-Madison)