Regulation of lipid metabolism by sphingolipids.

Sphingolipids, together with phospholipids and cholesterol are key components of membrane lipid bilayers, contribute to specialized membrane domains called rafts and function as signaling molecules. Sphingolipids have been recognized to exert a distinct role in the post-transcriptional regulation of the sterol-regulatory element binding proteins (SREBPs), key transcription factors of lipid synthesis. Sphingolipid synthesis is an obligate activator of SREBP. Inhibition of sphingolipid synthesis decreases SREBP on a post-transcriptional level. With the exception of enzymes that synthesize sphingolipids, SREBPs regulate the transcription of key enzymes that synthesize cholesterol, phospholipids and fatty acids. This observation suggests an exclusive role for sphingolipids in the regulation of lipid metabolism. Although exact mechanisms how sphingolipids regulate lipid metabolism are currently not known, this relationship has important implications with regard to cellular lipid homeostasis, composition of lipoproteins and development of atherosclerosis.