Glycosphingolipids and Metabolic Syndrome

Insulin resistance is associated with the lipid oversupply in obesity and as such has motivated the search for lipid mediators that can interfere with insulin signaling and glucose homeostasis. One class of lipids elevated in tissues of obese humans and rodents include the (glyco)sphingolipids suggesting these bioactive lipids may play a crucial role in insulin resistance.  We recently demonstrated that in animal models pharmacological reduction of glycosphingolipid biosynthesis ameliorates insulin resistance and prevents some manifestations of metabolic syndrome thereby supporting this concept. Since the critical (glyco)sphingolipid entities and their mechanisms are still uncertain, a systems biology approach is needed to complement classic biochemistry in understanding the role of glycosphingolipids in insulin resistance.