The Role of Ceramides in Diabetes and Cardiovascular Disease

The last quarter-century of research has dispelled the notion that sphingolipids are simply structural molecules involved in membrane bilayer formation. Certain sphingolipids, particularly the ceramides, are important intracellular messengers that have potent actions on cellular metabolism. Comprising amino and fatty acids, they are optimally poised to gauge the nutritional status of cells and organisms. In a modern epidemic of overnutrition and obesity-driven diseases, sphingolipids have emerged as potent biomarkers of heart disease and diabetes. Moreover, the ceramides play causal roles in multiple facets of cardiac and metabolic disease. Preventing nutrient-induced overload of ceramides prevents or reverses insulin resistance, β -cell failure, mitochondrial dysfunction, atherosclerosis, fatty liver disease, and heart failure. As a field, we are beginning to understand which of sphingolipid metabolites are most deleterious, where they act, and what mechanisms link them to cellular dysfunction. This knowledge has fueled efforts to target ceramide biosynthetic or degrading enzymes in order to treat or prevent diabetes and its associated co-morbidities. With the help of leading colleagues in the field, we provide an overview of ceramides as biomarkers and drivers of cardiac and metabolic disease.