A world of sphingolipids and glycolipids in the brain--novel functions of simple lipids modified with glucose.

Glycosphingolipids (GSLs) are present on cell surface membranes and are particularly abundant in the brain. Since over 300-400 GSLs are synthesized from glucosylceramide (GlcCer), GlcCer is believed to only serve as the source of most GSLs, including sialic acid-containing GSLs or gangliosides, in the brain. Recent studies, however, suggest that GlcCer itself plays a role in the heat stress response, as it functions as a glucose donor for the synthesis of cholesterylglucoside, a lipid mediator in heat stress responses in animals. GlcCer in adipose tissues is also thought to be involved in mechanisms that regulate energy (sugar and lipid) metabolism. Our extensive structural study revealed an additional novel glucosylated membrane lipid, called phosphatidylglucoside, in developing rodent brains and human neutrophils. These lipids, all modified with glucose, are enriched in lipid rafts and play important roles in basic cellular processes. Here, I summarize the recent progress regarding these glucosylated lipids and their biosynthesis and regulation in the central nervous system (CNS).