NMR characterization of the environmental regulation of lipid metabolism in C. elegans.

HERNÁNDEZ-CRAVERO, BRUNO; GASTÓN PREZ; LOMBARDO, VERÓNICA A.; BINOLFI, ANDRES; DE MENDOZA, DIEGO

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica.; 2022

Unsaturated fatty acids (UFAs) 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. Nevertheless, current methodologies fail tracking the chemical makeup of UFAs induced by external perturbations in live animals. To solve that, we introduce a high-resolution multidimensional nuclear magnetic resonance (NMR)approach to quantify unsaturated fatty acids (UFAs) in live Caenorhabditis elegans. By using uniform 13C isotope labeling and real-time 2D heteronuclear NMR spectroscopy in live worms we delineated their UFA compositions and the dynamic response of these fatty acids during cold adaptation. This methodology allowed us to monitor in real time the upregulation of UFA synthesis when ambient temperature is decreased. In addition, we describe how PAQR-2 signaling influences this central aspect of UFAs homeostasis in live worms analyzing UFAs synthesis in worms lacking the adiponectin receptor AdipoR2 homolog PAQR-2 during a temperature drop which supports the pivotal role of this protein in low temperature adaptation and survival. Overall, we provide a methodological framework for studying the dynamics of fatty acid desaturation in live C. elegans, which opens new research avenues to characterize genetic, environmental, dietary and pharmacological effects on UFA composition and biosynthesis.