Sphingolipid mediators of cell signaling and metabolism

Sphingolipids belong to a relatively minor class of lipid species in mammalian cells, but they have gained considerable attention recently because of emerging evidence that links them with lipotoxicity and a reduction of insulin sensitivity. This chapter summarizes our recent understanding of the role of different sphingolipid derivatives in cell-signaling responses and their role in the pathogenesis of metabolic diseases, including type 2 diabetes and cardiovascular disorders. We also provide an overview of the role of sphingolipids in the control of lipotoxicity at the molecular and cellular levels and relevant animal models and human studies. We also discuss mutual relationships between the actions of sphingolipids and obesity, insulin resistance, muscle function, β-cell exhaustion, the inflammatory response, vascular complications, and cardiac failure. A better awareness of sphingolipid metabolism may reveal potential pharmacological targets for the treatment of obesity-derived type 2 diabetes and other metabolic disorders.