Sphingolipids: players in the pathology of metabolic disease

The contribution of aberrant production of bioactive lipids to pathophysiological changes associated with obesity has risen to the forefront of lipid research. Increased diacylglycerol has been appreciated as a cause of insulin resistance, but emerging data support a role for sphingolipids in other metabolic diseases including obesity, diabetes, atherosclerosis and metabolic syndrome. Recent data demonstrate that elevation of plasma free fatty acids promotes aberrant sphingolipid production and composition in various tissues including skeletal muscle, pancreas and adipocytes. Moreover, rectifying these aberrant sphingolipid profiles often attenuates pathologies associated with their production. Although data thus far generate more questions than they answer, they indicate a major contribution of sphingolipids to pathologies associated with obesity. This review summarizes recent work in these areas.