Marta Moreno - A metabolomics approach to uncover the role of sphingolipids in metabolic diseases

The most fundamental challenge for all living organisms is to sense and respond to nutrient-derived signals in order to adapt their metabolism and physiology to promote survival and achieve balanced growth. Thus, synthesis and metabolism of a large variety of metabolites and macromolecules must be strictly coordinated to meet the nutritional requirements of cells and organisms.

Ceramides are increasingly being recognized as universal regulators of biological stress responses, and have been found to accumulate in individuals that display obesity and insulin resistance. Once ceramide levels rise above a critical threshold, tissues become insulin resistant and thus compromises nutrient uptake and storage. Prevention of ceramide accumulation in rodents improves insulin sensitivity and prevents the onset of metabolic disorders including diabetes, steatohepatitis and atherosclerosis.

The overall aim of the present proposal is to delineate how increased caloric intake in mammals affects the activities of metabolic pathways leading to increased de novo ceramide synthesis, which consequently perturbs central metabolic pathways. Using cutting edge bioanalytical and computational techniques we will discover how obesogenic diets affects signaling mechanisms and molecular networks, central to maintaining cellular lipid homeostasis. These insights will have implications for our general understanding of fundamental biochemical processes and for development of novel therapeutic strategies in obesity and diabetes.