Sphingosine Kinases/Sphingosine 1-Phosphate Signaling in Hepatic Lipid Metabolism.

The ever-increasing prevalence of metabolic diseases such as dyslipidemia and diabetes in the western world continues to be of great public health concern. Biologically active sphingolipids, such as sphingosine 1-phosphate (S1P) and ceramide, are important regulators of lipid metabolism. S1P not only directly functions as an active intracellular mediator, but also activates multiple signaling pathways via five transmembrane G-protein coupled receptors (GPCRs), S1PR1-5. S1P is exclusively formed by sphingosine kinases (SphKs). Two isoforms of SphKs, SphK1 and SphK2, have been identified. Recent identification of the conjugated bile acid-induced activation of S1PR2 as a key regulator of SphK2 opened new directions for both the sphingolipid and bile acid research fields. The role of SphKs/S1P-mediated signaling pathways in health and various human diseases has been extensively reviewed elsewhere. This review focuses on recent findings related to SphKs/S1P-medaited signaling pathways in regulating hepatic lipid metabolism.