Contribution of sphingolipids to the pathogenesis of obesity

Insulin resistance, Type 2 diabetes and accelerated atherosclerosis are common health complications associated with obesity, and increasing evidence suggest that a complex proinflammatory state together with increased lipid accumulation in extra adipose tissues, such as the liver and skeletal muscle, may contribute to the pathogenesis of these obesity-related disorders. Obesity-mediated inflammation is characterized by the elevated expression of proinflammatory molecules, primarily by the adipose tissues, by increased circulating concentrations of proinflammatory and prothrombotic proteins, cytokines and chemokines, free fatty acids, and the activation of pathways that regulate inflammation, including the c-Jun N-terminal kinase and NF-kappa B pathways. How these inter-related phenomena may be mechanistically linked is an important question. Recent evidence demonstrates that sphingolipid metabolism is altered in obesity and that these lipid mediators may provide a common pathway that link both excess nutrients and inflammation to increased metabolic and cardiovascular risk. This review highlights the contribution of sphingolipids, including ceramide, glucosylceramide and sphingosine 1 phosphate, to the pathogenesis of obesity and its related complications.