Study of fatty acids metabolism utilizing in vivo RMN in Caenorhabditis elegans

BRUNO HERNÁNDEZ CRAVERO; ANDRÉS BINOLFI ; GASTÓN PREZ; DIEGO DE MENDOZA; VERÓNICA A. LOMBARDO

Rosario

Congreso; Second Latin American Worm Meeting; 2020

The Latin American Worm Society

Caenorhabditis Elegans is a widely used model organism to characterize the molecular events involved in the progression of human diseases and a powerful resource for the design and validation of novel strategies for therapeutic intervention. One of the main advantages of this organism is that a diversity of disease triggering proteins and metabolic processes have orthologous genes and pathways that are highly conserved in the worm. Beside, fatty acids regulate central cellular process and perturbations of fatty homeostasis contribute to the onset of severe cardiovascular and neurodegenerative disorders, such as myocardial infarction, Alzheimers´ and Parkinson´s diseases. To advance the understanding of the roles of fatty acids in disease progression we ought to characterize their precise compositions under different conditions with the highest resolution possible in vivo. To do that, we introduce a high-resolution multidimensional nuclear magnetic resonance (NMR) approach to quantify unsaturated fatty acids (UFAs) in live C. elegans. By using 13C isotopically-enriched wild-type and mutants C. elegans strains with impaired UFAs biosynthesis we delineated their compositions and identified perturbations of fatty acid pools. We have also used this strategy to investigate the temperature regulation of UFAs synthesis. This innovative approach represents the first attempt to study the metabolic control fatty acids dynamics in a live animal with atomic resolution. These results will provide new insights about the environmental regulation of unsaturated fatty acids and establish benchmarks for future investigations of fatty acid regulation under experimental conditions that recapitulate human cardiovascular and neurodegenerative disorders.