PhD thesis defence by Anna Marqueño Bassols
Title: New tools for the detection of lipid disruptors and environmental obesogens
Director: Dr. Cinta Porte Visa
Lipidomics is one of the newest omics sciences, which has proven their utility in medical research for the discovery of biomarkers and altered metabolic pathways related to disease. Its application in environmental sciences is becoming relevant due to the important role of lipids in development, maintenance, and reproduction of metazoans. At the cellular level, lipids are involved in energy storage, signaling, and exhibit structural functions. Organisms contain thousands of different lipid species with rather similar structures. The latest advances in mass spectrometry have prompted the field of lipidomics, allowing a better annotation of the lipid species of different biological matrices (cells, biofluids, tissues), but also the detection of alterations as a response to chemical pollution exposure.
Three analytical techniques based on high-resolution mass spectrometry have been used for the characterization of the lipid profile of different biological models. The first method, flow injection analysis coupled to high-resolution mass spectrometry represents a powerful tool since, just in two minutes, it provides a quick screening of the lipid profile of cellular lipids. The other two methods, which incorporate ultra-high performance liquid chromatography for the previous separation of the lipids, have allowed the detection of minority species, and the application of tandem mass spectrometry together with an untargeted approach for data processing provided a more comprehensive lipid profile, together with the confirmation of lipid identities.
These analytical techniques have been used for the study of the impact of several widespread environmental pollutants on the lipid metabolism of both human and fish cell models, comprising plastic additives (BPA, BPF, BADGE, BADGE·H2O, BADGE·2HCl), the obesogenic compound tributyltin, all-trans retinoic acid, the synthetic progestin drospirenone and a complex mixture of environmental pollutants (field study). Lipidomics, together with some toxicological assays and the use of real-time polymerase chain reaction have allowed drawing a more complete scenario of the toxicological effects of the chemicals under study. Overall, this thesis aims to contribute to the use of lipidomics in environmental research by proposing useful biological models and workflows for the characterization of the mode of action of environmental pollutants with the capability to act as lipid disruptors.