AN UPDATE ON THE DEVELOPMENT OF AN AUTOMATED LIPIDOMICS METHOD AND ITS POTENTIAL AS AN ENVIRONMENTAL HEALTH ASSESSMENT TOOL

John A. Bowden, Bruce Blumberg, Louis Guillette, Michele Schantz, and John Kucklick

Lipids present a unique target for disease state biomarkers, mainly due to the fact that they are ubiquitous (present at membrane, cellular, tissue and systemic levels) and exhibit a variety of roles (development, reproduction, immune response and cell signaling). Since the inception of lipidomics-based methods, lipidomics has been successfully applied for disease discovery and for an increased understanding of the etiology of Alzheimer’s disease, diabetes, heart disease and certain types of cancers. While the traditional platform for lipidomics has generally been limited to clinical/medical-based studies, the application of lipidomics to environmental health presents a promising direction. The research described presents the recent progress in developing lipidomics as an environmental health assessment tool, which includes 1) the development of an automated lipidomics approach, 2) an investigation of suitable lipidomics reference materials, 3) the analysis of lipid alterations from a TBT/mouse exposure model and 4) the application of the lipidomics technique to dolphin populations with varying contaminant exposure histories.

An unconventional automated lipidomics approach (1) was designed by applying a liquid chromatography autosampler to draw up discrete amounts of sample and slowly dispense the sample into the mass spectrometer (MS) using user-defined sample volumes and flow rates (allowing for extended acquisition periods). In addition to saving analysis time, the automated method also allowed for more consistent data collection and a reduction in sample crosstalk.

As varied and as widely used as reference materials have become, the concept of using reference materials (2) in the field of lipidomics has not been fully explored. Here, we examined various plasmas, tissues, and lipid extracts as potential lipidomics reference materials. The aim of this study was to demonstrate the potential benefit of using reference materials in lipid analysis and to highlight their role in improving the confidence of current lipid measurements.

To date, there are no published studies using mass spectrometry to assess the impact of obesogen exposure on lipid metabolism. Using the developed lipidomic/mass spectrometry-based methods described and a TBT exposure/mouse model (3), specific global, class, and individual lipid alterations were highlighted between treatment groups and sexes.

The use of lipidomics on dolphin samples from wild populations (4) with varying contaminant exposure histories is the first study to apply lipidomics as an environmental health assessment tool. Initial results suggest that there are fundamental lipid differences among dolphins from different locations (i.e., varying exposure histories). The preliminary data has resulted in a greater commitment towards continuing the on-going examination into the potential lipid/contaminant relationship that may be used with non-invasive sampling techniques to assess both short- and long-term exposures on a population level.